cholinergic receptors

Summary

Summary: Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology.

Top Publications

  1. ncbi The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo
    T M DeChiara
    Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591, USA
    Cell 85:501-12. 1996
  2. ncbi Distinct domains of MuSK mediate its abilities to induce and to associate with postsynaptic specializations
    H Zhou
    Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Cell Biol 146:1133-46. 1999
  3. ncbi Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy
    A E Deconinck
    Department of Biochemistry, University of Oxford, United Kingdom
    Cell 90:717-27. 1997
  4. ncbi LRP4 serves as a coreceptor of agrin
    Bin Zhang
    Program of Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA
    Neuron 60:285-97. 2008
  5. ncbi MuSK controls where motor axons grow and form synapses
    Natalie Kim
    Molecular Neurobiology Program, The Helen L and Martin S Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University Medical School, New York, NY 10016, USA
    Nat Neurosci 11:19-27. 2008
  6. ncbi Acetylcholine receptors loss and postsynaptic damage in MuSK antibody-positive myasthenia gravis
    Hirokazu Shiraishi
    The First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki, Japan
    Ann Neurol 57:289-93. 2005
  7. ncbi The role of nerve- versus muscle-derived factors in mammalian neuromuscular junction formation
    Shuo Lin
    Biozentrum, University of Basel, CH 4056 Basel, Switzerland
    J Neurosci 28:3333-40. 2008
  8. ncbi Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis
    Amelia Evoli
    Department of Neuroscience, Catholic University, Roma, Italy
    Brain 126:2304-11. 2003
  9. ncbi Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin
    L V Borovikova
    The Picower Institute for Medical Research, Manhasset, New York 11030, USA
    Nature 405:458-62. 2000
  10. ncbi The in vitro and in vivo phosphotyrosine map of activated MuSK
    A Watty
    Molecular Neurobiology Program, Skirball Institute, New York University Medical School, 540 First Avenue, New York, NY 10016, USA
    Proc Natl Acad Sci U S A 97:4585-90. 2000

Detail Information

Publications266 found, 100 shown here

  1. ncbi The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo
    T M DeChiara
    Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591, USA
    Cell 85:501-12. 1996
    ....
  2. ncbi Distinct domains of MuSK mediate its abilities to induce and to associate with postsynaptic specializations
    H Zhou
    Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Cell Biol 146:1133-46. 1999
    ..These interactions allow MuSK not only to induce a multimolecular AChR-containing complex, but also to localize that complex to a primary scaffold in the postsynaptic membrane...
  3. ncbi Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy
    A E Deconinck
    Department of Biochemistry, University of Oxford, United Kingdom
    Cell 90:717-27. 1997
    ..Detailed study of these mice should provide novel insights into the pathogenesis of DMD and provide an improved model for rapid evaluation of gene therapy strategies...
  4. ncbi LRP4 serves as a coreceptor of agrin
    Bin Zhang
    Program of Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA
    Neuron 60:285-97. 2008
    ..These observations indicate that LRP4 is a coreceptor of agrin that is necessary for MuSK signaling and AChR clustering and identify a potential target protein whose mutation and/or autoimmunization may cause muscular dystrophies...
  5. ncbi MuSK controls where motor axons grow and form synapses
    Natalie Kim
    Molecular Neurobiology Program, The Helen L and Martin S Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University Medical School, New York, NY 10016, USA
    Nat Neurosci 11:19-27. 2008
    ....
  6. ncbi Acetylcholine receptors loss and postsynaptic damage in MuSK antibody-positive myasthenia gravis
    Hirokazu Shiraishi
    The First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki, Japan
    Ann Neurol 57:289-93. 2005
    ..MuSK antibodies do not appear to cause substantial AChR loss, complement deposition, or morphological damage. Effects on MuSK function need to be explored...
  7. ncbi The role of nerve- versus muscle-derived factors in mammalian neuromuscular junction formation
    Shuo Lin
    Biozentrum, University of Basel, CH 4056 Basel, Switzerland
    J Neurosci 28:3333-40. 2008
    ..A model is proposed that explains either the neurocentric or the myocentric mode of NMJ formation depending on a balance between the levels of MuSK expression and the availability of nerve-released agrin...
  8. ncbi Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis
    Amelia Evoli
    Department of Neuroscience, Catholic University, Roma, Italy
    Brain 126:2304-11. 2003
    ....
  9. ncbi Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin
    L V Borovikova
    The Picower Institute for Medical Research, Manhasset, New York 11030, USA
    Nature 405:458-62. 2000
    ..Direct electrical stimulation of the peripheral vagus nerve in vivo during lethal endotoxaemia in rats inhibited TNF synthesis in liver, attenuated peak serum TNF amounts, and prevented the development of shock...
  10. ncbi The in vitro and in vivo phosphotyrosine map of activated MuSK
    A Watty
    Molecular Neurobiology Program, Skirball Institute, New York University Medical School, 540 First Avenue, New York, NY 10016, USA
    Proc Natl Acad Sci U S A 97:4585-90. 2000
    ..Our biochemical data are consistent with results from functional experiments and establish a good correlation between tyrosine residues that are phosphorylated in activated MuSK and tyrosines that are required for MuSK signaling...
  11. ncbi Chronic aspartame affects T-maze performance, brain cholinergic receptors and Na+,K+-ATPase in rats
    Brandon Christian
    Department of Pharmacology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA
    Pharmacol Biochem Behav 78:121-7. 2004
    ..Using [(3)H]quinuclidinyl benzilate (QNB) (1 nM) to label muscarinic cholinergic receptors and atropine (10(-6) M) to determine nonspecific binding in whole-brain preparations, aspartame-treated ..
  12. ncbi Impaired synaptic vesicle release and immaturity of neuromuscular junctions in spinal muscular atrophy mice
    Lingling Kong
    Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA
    J Neurosci 29:842-51. 2009
    ..Together these results indicate that impaired synaptic vesicle release at NMJs in severe SMA is likely to contribute to failed postnatal maturation of motor units and muscle weakness...
  13. ncbi Postsynaptic abnormalities at the neuromuscular junctions of utrophin-deficient mice
    A E Deconinck
    Department of Biochemistry, University of Oxford, United Kingdom
    J Cell Biol 136:883-94. 1997
    ..Defects of utrophin could underlie some forms of congenital myasthenic syndrome in which a reduction of postsynaptic folds is observed...
  14. ncbi Tyrosine-phosphorylated and nonphosphorylated isoforms of alpha-dystrobrevin: roles in skeletal muscle and its neuromuscular and myotendinous junctions
    R Mark Grady
    Dept of Pediatrics, Washington University School of Medicine, Pediatric Research Bldg, St Louis, MO 63110, USA
    J Cell Biol 160:741-52. 2003
    ..More generally, alphaDB may play multiple roles in muscle by means of differential distribution of isoforms with distinct signaling or structural properties...
  15. ncbi Agrin-induced phosphorylation of the acetylcholine receptor regulates cytoskeletal anchoring and clustering
    L S Borges
    Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3A 2T5, Canada
    J Cell Biol 153:1-12. 2001
    ....
  16. ncbi A mammalian homolog of Drosophila tumorous imaginal discs, Tid1, mediates agrin signaling at the neuromuscular junction
    Jenny Linnoila
    Molecular Pharmacology Graduate Training Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Neuron 60:625-41. 2008
    ..These results demonstrate that Tid1 is an essential component of the agrin signaling pathway, crucial for synaptic development...
  17. ncbi Assembly of the postsynaptic membrane at the neuromuscular junction: paradigm lost
    Terrance T Kummer
    Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA
    Curr Opin Neurobiol 16:74-82. 2006
    ..These recent studies challenge the widely-held paradigms, although not the results that led to them, and suggest a new model for neuromuscular synaptogenesis...
  18. ncbi Impaired off-line consolidation of motor memories after combined blockade of cholinergic receptors during REM sleep-rich sleep
    Björn Rasch
    Department of Neuroendocrinology, University of Lubeck, Lubeck, Germany
    Neuropsychopharmacology 34:1843-53. 2009
    ..Taken together, these results identify high cholinergic activity during late, REM sleep-rich sleep as an essential factor promoting sleep-dependent consolidation of motor skills...
  19. ncbi Identification of an element crucial for the sub-synaptic expression of the acetylcholine receptor epsilon-subunit gene
    A Duclert
    URA CNRS 0210 Neurobiologie Moleculaire, Departement des Biotechnologies, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
    J Biol Chem 271:17433-8. 1996
    ..The identification of such a site opens the possibility to identify regulatory factors responsible for compartmentalized expression at the neuromuscular junction...
  20. ncbi Lithocholyltaurine interacts with cholinergic receptors on dispersed chief cells from guinea pig stomach
    J P Raufman
    Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205 7199, USA
    Am J Physiol 274:G997-1004. 1998
    ..Half-maximal inhibition of [3H]NMS binding was observed with approximately 0.5 mM carbachol and 1 mM LCT. These results indicate that the bile acid LCT is a partial agonist for muscarinic cholinergic receptors on gastric chief cells.
  21. ncbi Induction of multiple signaling loops by MuSK during neuromuscular synapse formation
    C Moore
    Department of Physiology, University of Basel, 4051 Basel, Switzerland
    Proc Natl Acad Sci U S A 98:14655-60. 2001
    ..In this way, MuSK activation leads to the establishment of a neuregulin-1-dependent signaling complex that maintains MuSK, ErbB, and AChR expression at the synapse of electrically active muscle fibers...
  22. ncbi Combined blockade of cholinergic receptors shifts the brain from stimulus encoding to memory consolidation
    Björn H Rasch
    University of Lubeck, Germany
    J Cogn Neurosci 18:793-802. 2006
    ....
  23. ncbi Expression of mutant Ets protein at the neuromuscular synapse causes alterations in morphology and gene expression
    Alban de Kerchove d'Exaerde
    Laboratoire de Neurobiologie Moléculaire, CNRS URA 2182 Récepteurs et Cognition Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
    EMBO Rep 3:1075-81. 2002
    ..They further show that Ets-independent mechanisms control the synaptic expression of a distinct set of synaptic genes...
  24. ncbi The Agrin/MuSK signaling pathway is spatially segregated from the neuregulin/ErbB receptor signaling pathway at the neuromuscular junction
    J C Trinidad
    Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 20:8762-70. 2000
    ..The differential distributions of the neuregulin and agrin signaling pathways argue against neuregulin and erbB receptors being localized to the NMJ via direct interactions with either agrin or MuSK...
  25. ncbi Acetylcholine receptor clustering and triton solubility: neural effect
    T R Podleski
    Section of Neurobiology and Behavior, Cornell University, Ithaca, New York 14853
    J Neurobiol 19:167-85. 1988
    ....
  26. ncbi Zebrafish unplugged reveals a role for muscle-specific kinase homologs in axonal pathway choice
    Jing Zhang
    Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6058, USA
    Nat Neurosci 7:1303-9. 2004
    ..Our results demonstrate a new role for MuSK homologs in axonal pathway selection...
  27. ncbi Laminin and alpha7beta1 integrin regulate agrin-induced clustering of acetylcholine receptors
    D J Burkin
    Department of Cell and Structural Biology, University of Illinois, Urbana, IL 61801, USA
    J Cell Sci 113:2877-86. 2000
    ....
  28. ncbi Maintenance of acetylcholine receptor number by neuregulins at the neuromuscular junction in vivo
    A W Sandrock
    Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
    Science 276:599-603. 1997
    ..Thus, the density of AChRs in the postsynaptic membrane depends on immunoglobulin-containing neuregulin isoforms throughout the life of the animal...
  29. ncbi Pre- and postsynaptic maturation of the neuromuscular junction during neonatal synapse elimination depends on protein kinase C
    Maria A Lanuza
    Unitat d Histologia i Neurobiologia UHN, Facultat de Medicina i Ciencies de la Salut, Universitat Rovira i Virgili, Reus, Spain
    J Neurosci Res 67:607-17. 2002
    ..PKC may act primarily to influence AChR clusters and not axons, insofar as phorbol ester activation of PKC accelerated changes in receptor aggregates but produced relatively little axon loss...
  30. ncbi The role of the dorsal raphe-serotonergic system and cholinergic receptors in the modulation of working memory
    S Ruotsalainen
    A I Virtanen Institute, University of Kuopio, Finland
    Neurosci Biobehav Rev 22:21-31. 1998
    ..significantly impair the choice accuracy or interfere with motor activity of rats; (ii) the blockade of cholinergic receptors does not impair working memory per se, but disrupts motor activity, and (iii) pCA lesion of serotonergic ..
  31. ncbi Morphine-induced place preference: involvement of cholinergic receptors of the ventral tegmental area
    Ameneh Rezayof
    School of Biology, University College of Science, University of Tehran, Tehran, Iran
    Eur J Pharmacol 562:92-102. 2007
    ..We conclude that muscarinic and nicotinic acetylcholine receptors in the ventral tegmental area may critically mediate the rewarding effects of morphine...
  32. ncbi Rescue of the cardiac defect in ErbB2 mutant mice reveals essential roles of ErbB2 in peripheral nervous system development
    J K Morris
    The Salk Institute, La Jolla, California 92037, USA
    Neuron 23:273-83. 1999
    ..However, these clusters are dispersed and morphologically different from those in control muscle. Our results reveal an important role for erbB2 during normal peripheral nervous system development...
  33. ncbi The expression and biological role of the non-neuronal cholinergic system in the ovary
    Artur Mayerhofer
    Anatomisches Institut der Universität München, Biedersteiner Strasse 29, D 80802 München, Germany
    Life Sci 72:2039-45. 2003
    ..We propose that an as yet unexplored intraovarian cholinergic system exists, which contributes to physiological ovarian tissue remodeling by stimulation of cell proliferation...
  34. ncbi MuSK induces in vivo acetylcholine receptor clusters in a ligand-independent manner
    A Sander
    Abteilung Zellphysiologie, Max Planck Institut fur medizinische Forschung, D 69120 Heidelberg, Germany
    J Cell Biol 155:1287-96. 2001
    ..Thus, the kinase activity of MuSK initiates signals that are sufficient to induce the formation of AChR clusters. This process does not require additional determinants located in the ectodomain...
  35. ncbi Interaction of chlorphenvinphos with cholinergic receptors in the rabbit hypothalamus
    S Gralewicz
    Nofer Institute of Occupational Medicine, Laboratory of Neurotoxicity Evaluation, Lodz, Poland
    Neurotoxicol Teratol 17:289-95. 1995
    ..to find out whether chlorphenvinphos (CVP), an organophosphorous pesticide, interacts with the muscarinic cholinergic receptors in CNS...
  36. ncbi Development of the neuromuscular junction
    Veit Witzemann
    Max Planck Institut fur medizinische Forschung, Jahnstrasse 29, 69120 Heidelberg, Germany
    Cell Tissue Res 326:263-71. 2006
    ....
  37. ncbi Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse
    W Lin
    The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
    Nature 410:1057-64. 2001
    ..In contrast, the subsequent stages of synaptic growth and maintenance require nerve-derived agrin, and a second nerve-derived signal that disperses ectopic postsynaptic apparatus...
  38. ncbi Agrin acts via a MuSK receptor complex
    D J Glass
    Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591, USA
    Cell 85:513-23. 1996
    ..Here we demonstrate that agrin acts via a receptor complex that includes MuSK as well as a myotube-specific accessory component...
  39. ncbi Aberrant patterning of neuromuscular synapses in choline acetyltransferase-deficient mice
    Eugene P Brandon
    Laboratory of Genetics and Peptide Biology Laboratories, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    J Neurosci 23:539-49. 2003
    ..These results indicate that ChAT is uniquely essential for the patterning and formation of mammalian neuromuscular synapses...
  40. ncbi Neuromuscular synapses can form in vivo by incorporation of initially aneural postsynaptic specializations
    Heather Flanagan-Steet
    Department of Anatomy and Neurobiology, Washington University Medical School, St Louis, MO 63110, USA
    Development 132:4471-81. 2005
    ..Moreover, many AChR clusters on later-born fast muscle fibers formed at sites that had already been contacted by axons, suggesting heterogeneity in the signaling mechanisms leading to synapse formation by a single axon...
  41. ncbi The relationship between perlecan and dystroglycan and its implication in the formation of the neuromuscular junction
    H B Peng
    Department of Cell Biology and Anatomy, University of North Carolina, Chapel Hill 27599 7090, USA
    Cell Adhes Commun 5:475-89. 1998
    ..This competition may result in the presentation of perlecan-bound growth factors such as HB-GAM to effect synaptic induction...
  42. ncbi Blockade of central cholinergic receptors impairs new learning and increases proactive interference in a word paired-associate memory task
    Alireza Atri
    Boston University, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02215, USA
    Behav Neurosci 118:223-36. 2004
    Experimental data and computational models suggest that blockade of muscarinic cholinergic receptors impairs paired-associate learning and increases proactive interference (E. DeRosa & M. E. Hasselmo, 2000; M. E. Hasselmo & J. M...
  43. ncbi Gating of acetylcholine receptor channels: brownian motion across a broad transition state
    Anthony Auerbach
    Center for Single Molecule Biophysics and the Department of Physiology and Biophysics, State University of New York, 324 Cary Hall, Buffalo, NY 14214, USA
    Proc Natl Acad Sci U S A 102:1408-12. 2005
    ..The results suggest that the coarse-grained AChR gating conformational change propagates through the protein with dynamics that are governed by the Brownian motion of individual gating blocks...
  44. ncbi Congenital myasthenic syndromes and the formation of the neuromuscular junction
    David Beeson
    Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
    Ann N Y Acad Sci 1132:99-103. 2008
    ....
  45. ncbi Nerve terminals form but fail to mature when postsynaptic differentiation is blocked: in vivo analysis using mammalian nerve-muscle chimeras
    Q T Nguyen
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 20:6077-86. 2000
    ..Normal postsynaptic differentiation appears to be dispensable for initial stages of presynaptic differentiation but required for presynaptic maturation...
  46. ncbi Syne-1, a dystrophin- and Klarsicht-related protein associated with synaptic nuclei at the neuromuscular junction
    E D Apel
    Department of Anatomy and Neurobiology and Department of Pediatrics, Washington University Medical School, St Louis, Missouri 63110, USA
    J Biol Chem 275:31986-95. 2000
    ..Finally, we identify a homologous gene, syne-2, that is expressed in an overlapping but distinct pattern...
  47. ncbi AChR phosphorylation and indirect inhibition of AChR function in seronegative MG
    C P Plested
    Neurosciences Group, Department of Clinical Neurology, Weatherall Institute of Molecular Medicine, University of Oxford, UK
    Neurology 59:1682-8. 2002
    ..Identifying the target for this factor should lead to improved diagnosis of MG in MuSK antibody-negative patients and may provide new insights into the function of the neuromuscular junction and pathophysiological mechanisms in MG...
  48. ncbi Neurotransmitter acetylcholine negatively regulates neuromuscular synapse formation by a Cdk5-dependent mechanism
    Weichun Lin
    The Salk Institute, La Jolla, California 92037, USA
    Neuron 46:569-79. 2005
    ..Genetic elimination of Cdk5 or blocking ACh production prevents the dispersion of AChR clusters in agrin mutants. Therefore, we propose that ACh negatively regulates neuromuscular synapse formation through a Cdk5-dependent mechanism...
  49. ncbi Dynamics of the acetylcholine receptor pore at the gating transition state
    Ananya Mitra
    Center for Single Molecule Biophysics and Department of Physiology and Biophysics, University at Buffalo, State University of New York, Buffalo, NY 14214, USA
    Proc Natl Acad Sci U S A 102:15069-74. 2005
    ....
  50. ncbi Crystal structure of the MuSK tyrosine kinase: insights into receptor autoregulation
    Jeffrey H Till
    Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    Structure 10:1187-96. 2002
    ..These studies provide a molecular basis for understanding the regulation of MuSK catalytic activity and suggest that an additional in vivo component may contribute to regulation via the juxtamembrane region...
  51. ncbi Unravelling the pathogenesis of myasthenia gravis
    Angela Vincent
    Neurosciences Group, Department of Clinical Neurology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK
    Nat Rev Immunol 2:797-804. 2002
    ....
  52. ncbi Neuromuscular synaptogenesis: clustering of acetylcholine receptors revisited
    R Willmann
    Department of Neurochemistry, Brain Research Institute, , Switzerland
    Cell Mol Life Sci 59:1296-316. 2002
    ....
  53. ncbi Synapse disassembly and formation of new synapses in postnatal muscle upon conditional inactivation of MuSK
    Boris A Hesser
    Max Planck Institut fur medizinische Forschung, Jahnstrasse 29, 69120 Heidelberg, Germany
    Mol Cell Neurosci 31:470-80. 2006
    ..Thus, MuSK and AChR together maintain the functional and structural integrity of the postsynaptic architecture and prevent axon growth...
  54. ncbi Seronegative myasthenia gravis: disease severity and prognosis
    F Romi
    Department of Neurology, Haukeland University Hospital, Bergen, Norway
    Eur J Neurol 12:413-8. 2005
    ..With proper treatment, especially early thymectomy for seropositive MG, the outcome and long-term prognosis is good in patients with and without AChR antibodies...
  55. ncbi Initial phase 2 trial of a nicotinic agonist in schizophrenia
    Robert Freedman
    Department of Psychiatry, Denver VA Medical Center and University of Colorado, Denver, CO 80262, USA
    Am J Psychiatry 165:1040-7. 2008
    ..The agent 3-(2,4-dimethoxybenzylidene) anabaseine (DMXB-A) is a partial alpha(7)-nicotinic agonist and can be taken orally. A phase 1 trial showed evidence for cognitive enhancement in schizophrenia...
  56. ncbi Tyrosine phosphatase regulation of MuSK-dependent acetylcholine receptor clustering
    Raghavan Madhavan
    Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, SAR, Hong Kong, China
    Mol Cell Neurosci 28:403-16. 2005
    ..Our results suggest that muscle tyrosine phosphatases tightly regulate MuSK activation and signaling and support a novel role of Shp2 in MuSK-dependent AChR clustering...
  57. ncbi The dystroglycan complex is necessary for stabilization of acetylcholine receptor clusters at neuromuscular junctions and formation of the synaptic basement membrane
    C Jacobson
    Department of Biology, McGill University/Center for Neuroscience Research, , , , Canada
    J Cell Biol 152:435-50. 2001
    ..In addition, they suggest that dystroglycan functions in the organization and stabilization of AChR clusters, which appear to be mediated through its binding of laminin...
  58. ncbi In vivo imaging of preferential motor axon outgrowth to and synaptogenesis at prepatterned acetylcholine receptor clusters in embryonic zebrafish skeletal muscle
    Jessica A Panzer
    Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 26:934-47. 2006
    ..Thus, during initial synaptogenesis, postsynaptic differentiation precedes presynaptic differentiation, and prepatterned neurotransmitter clusters mark sites destined for synapse formation...
  59. ncbi Molecular regulation of postsynaptic differentiation at the neuromuscular junction
    Raghavan Madhavan
    Department of Biology, Hong Kong University of Science and Technology, Kowloon, Hong Kong, China
    IUBMB Life 57:719-30. 2005
    ..In this review we discuss how regulation of AChR re-distribution by multiple factors ensures aggregation of AChRs exclusively at NMJs...
  60. ncbi DNA topoisomerase IIbeta and neural development
    X Yang
    Skirball Institute of Molecular Medicine, New York University Medical School, 540 First Avenue, New York, NY 10016, USA
    Science 287:131-4. 2000
    ..The defects in motor axon growth in IIbeta mutant mice resulted in a breathing impairment and death of the pups shortly after birth...
  61. ncbi Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal gamma subunit
    Katrin Hoffmann
    Institute of Medical Genetics, Charite University Medical School, Humboldt University, 13353 Berlin, Germany
    Am J Hum Genet 79:303-12. 2006
    ....
  62. ncbi Differential involvement of M1-type and M4-type muscarinic cholinergic receptors in the dorsomedial striatum in task switching
    Martha F McCool
    Department of Psychology, Center for Cognitive Medicine, Laboratory of Integrative Neuroscience, University of Illinois at Chicago, Chicago, IL 60607, USA
    Neurobiol Learn Mem 89:114-24. 2008
    ..Further evidence indicates that muscarinic cholinergic receptors in this brain area support adaptations in behavioral responses...
  63. ncbi The role of loop 5 in acetylcholine receptor channel gating
    Sudha Chakrapani
    Center for Single Molecule Biophysics and Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY 14214, USA
    J Gen Physiol 122:521-39. 2003
    ..L5 emerges as an important and early link in the AChR gating reaction which, in the absence of agonist, serves to increase the relative stability of the closed conformation of the protein...
  64. ncbi Inhibition of synapse assembly in mammalian muscle in vivo by RNA interference
    Xian Chu Kong
    Biozentrum, University of Basel, Basel, Switzerland
    EMBO Rep 5:183-8. 2004
    ..Moreover, they show that MuSK is also required for the maintenance of the NMJ, offering a mechanistic explanation for the myasthenia gravis caused by auto-antibodies to MuSK...
  65. ncbi A quantitative fluorescence-imaging technique for studying acetylcholine receptor turnover at neuromuscular junctions in living animals
    S G Turney
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Neurosci Methods 64:199-208. 1996
    ....
  66. ncbi Detection and characterization of MuSK antibodies in seronegative myasthenia gravis
    John McConville
    Weatherall Institute of Molecular Medicine and Department of Clinical Neurology, Oxford, UK
    Ann Neurol 55:580-4. 2004
    ..They bind to the extracellular Ig-like domains of soluble or native MuSK. Surprisingly they are predominantly in the IgG4 subclass. MuSK-antibody associated MG may be different in etiological and pathological mechanisms...
  67. ncbi An amino-terminal extension is required for the secretion of chick agrin and its binding to extracellular matrix
    A J Denzer
    Department of Pharmacology, University of Basel, Switzerland
    J Cell Biol 131:1547-60. 1995
    ..In conclusion, the cDNAs described here code for chick agrin that has all the characteristics previously allocated to endogenous agrin...
  68. ncbi Laminin and alpha-dystroglycan mediate acetylcholine receptor aggregation via a MuSK-independent pathway
    F Montanaro
    Centre for Research in Neuroscience, McGill University, Montreal General Hospital Research Institute, Montreal, Canada H3G 1A4
    J Neurosci 18:1250-60. 1998
    ..We hypothesize that the interaction of LN with alpha-DG contributes to the growth and/or stabilization of AChR microaggregates into macroaggregates at the developing NMJ via a MuSK-independent mechanism...
  69. ncbi Structure and gating mechanism of the acetylcholine receptor pore
    Atsuo Miyazawa
    RIKEN Harima Institute, 1-1-1 Kouto, Mikazuki-cho, Sayo, Hyogo 679-5148, Japan
    Nature 423:949-55. 2003
    ..These rotations are communicated through the inner helices, and open the pore by breaking the girdle apart...
  70. ncbi Localization and regulation of MuSK at the neuromuscular junction
    D C Bowen
    Regeneron Pharmaceuticals, Tarrytown, New York 10591, USA
    Dev Biol 199:309-19. 1998
    ..Together, these findings demonstrate that MuSK expression is highly regulated by innervation, muscle activity, and agrin, while the distribution of MuSK is precisely coordinated with that of the AChR...
  71. ncbi Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia
    Anantha Shekhar
    Department of Psychiatry, Indiana University School of Medicine, 1111 West 10th St, Suite 313, Indianapolis, IN 46202, USA
    Am J Psychiatry 165:1033-9. 2008
    ..The authors studied xanomeline, a relatively selective muscarinic type 1 and type 4 (M(1) and M(4)) receptor agonist, to determine if this agent is effective in the treatment of schizophrenia...
  72. ncbi Cholinergic systems in progressive supranuclear palsy
    N M Warren
    Institute for Ageing and Health, University of Newcastle upon Tyne, UK
    Brain 128:239-49. 2005
    ..Symptomatic treatment using cholinergic drugs may thus be improved by more specific targeting of cholinergic receptors or nuclei. There is also evidence that cholinergic agents may have disease-modifying effects...
  73. ncbi Rapid and reversible effects of activity on acetylcholine receptor density at the neuromuscular junction in vivo
    M Akaaboune
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Science 286:503-7. 1999
    ..The rapid and reversible alterations in AChR density at the neuromuscular junction in vivo parallel changes thought to occur in the central nervous system at synapses undergoing potentiation and depression...
  74. ncbi Formation of the neuromuscular junction. Agrin and its unusual receptors
    W Hoch
    Max Planck Institut fur Entwicklungsbiologie, Abteilung Biochemie, Tubingen, Germany
    Eur J Biochem 265:1-10. 1999
    ..While many components of the machinery triggering postsynaptic differentiation have now been identified, our picture of the molecular pathway causing the redistribution of synaptic proteins is still incomplete...
  75. ncbi Pre- and post-synaptic abnormalities associated with impaired neuromuscular transmission in a group of patients with 'limb-girdle myasthenia'
    C R Slater
    School of Neurology, Neurobiology and Psychiatry, University of Newcastle upon Tyne, Bath, Newcastle upon Tyne, UK
    Brain 129:2061-76. 2006
    ....
  76. ncbi Acetylcholine receptor gating at extracellular transmembrane domain interface: the cys-loop and M2-M3 linker
    Archana Jha
    Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY 14214, USA
    J Gen Physiol 130:547-58. 2007
    ..The M2-M3 linker appears to be the key moving part that couples gating motions at the base of the ECD with those in TMD. These interactions are distributed along an approximately 16-A border and involve about a dozen residues...
  77. ncbi Muscle-wide secretion of a miniaturized form of neural agrin rescues focal neuromuscular innervation in agrin mutant mice
    Shuo Lin
    Biozentrum and Institute of Physiology, Department of Biomedicine, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland
    Proc Natl Acad Sci U S A 105:11406-11. 2008
    ..Finally, they suggest a novel local function of ACh in stabilizing postsynaptic structures...
  78. ncbi ATP potentiates agrin-induced AChR aggregation in cultured myotubes: activation of RhoA in P2Y1 nucleotide receptor signaling at vertebrate neuromuscular junctions
    Karen K Y Ling
    Department of Biology and Molecular Neuroscience Center, Hong Kong University of Science and Technology, Hong Kong, China
    J Biol Chem 279:31081-8. 2004
    ....
  79. ncbi Microcontact printing: a versatile technique for the study of synaptogenic molecules
    Toby Cornish
    Neuroscience Program, University of Illinois at Urbana-Champaign, Illinois 61801, USA
    Mol Cell Neurosci 20:140-53. 2002
    ..Our results demonstrate that microcontact printing is applicable to the analysis of cellular response to locally immobilized information molecules...
  80. ncbi Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1
    Zhen G Luo
    Department of Neurobiology, Civitan International Research Center, University of Alabama at Birmingham, 1530 Third Avenue South, Birmingham, AL 35294, USA
    Neuron 35:489-505. 2002
    ..Inhibition of PAK1 activity attenuates AChR clustering. These results demonstrate important roles of Dvl and PAK in Agrin/MuSK-induced AChR clustering and reveal a novel function of Dvl in synapse development...
  81. ncbi A novel pathway for MuSK to induce key genes in neuromuscular synapse formation
    Eric Lacazette
    Department of Physiology, University of Basel, CH 4056 Basel, Switzerland
    J Cell Biol 161:727-36. 2003
    ..The same pathways are used to regulate synaptic expression of AChR epsilon. We propose that the novel pathway stabilizes the synapse early in development, whereas the NRG/ErbB pathway supports maintenance of the mature synapse...
  82. ncbi The features of myasthenia gravis with autoantibodies to MuSK
    D Lavrnic
    The Institute of Neurology, Clinical Centre of Serbia, 11000 Belgrade, 6 Dr Subotica Street, Serbia and Montenegro
    J Neurol Neurosurg Psychiatry 76:1099-102. 2005
    ..To determine if myasthenia gravis (MG) with antibodies to MuSK is a distinct subgroup of seronegative MG...
  83. ncbi Autoimmune myasthenia gravis in childhood
    P Ian Andrews
    University of New South Wales, Australia
    Semin Neurol 24:101-10. 2004
    ..Clinical features, diagnostic methods, and management strategies pertinent to children with autoimmune myasthenia are discussed, as well as the emerging data regarding the anti-MuSK autoimmune process in myasthenia gravis...
  84. ncbi Regulation of acetylcholine receptor clustering by the tumor suppressor APC
    Junmei Wang
    Department of Neurobiology, University of Pittsburgh School of Medicine, 3500 Terrace Street, Room E1440 BST, Pittsburgh, Pennsylvania 15261, USA
    Nat Neurosci 6:1017-8. 2003
    ..We report here that the mouse tumor suppressor protein adenomatous polyposis coli (APC) has a role in AChR clustering and that the Wnt/beta-catenin pathway may crosstalk with agrin signaling cascade during synapse formation...
  85. ncbi Seronegative myasthenia gravis
    Angela Vincent
    Department of Clinical Neurology, University of Oxford, Oxford, United Kingdom
    Semin Neurol 24:125-33. 2004
    ..MuSK antibody-positive patients may also differ in the distribution of their electrophysiological abnormalities and their responses to treatments...
  86. ncbi Effect of D-penicillamine on neuromuscular junction in patients with Wilson disease
    R N Komal Kumar
    Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
    Neurology 63:935-6. 2004
  87. ncbi Molecular dissection of neuromuscular junction formation
    Werner Hoch
    University of Houston, Science and Research Building 2, Houston, TX 77204 5001, USA
    Trends Neurosci 26:335-7. 2003
    ..Analysis of the imperfect postsynaptic specializations of these mice has provided new insights into the complex postsynaptic differentiation process...
  88. ncbi [Myasthenia gravis induced by autoantibodies against MuSK]
    Kazuhiro Shigemoto
    Research Team for Molecular Biomarkers, Tokyo Metropolitan Institute of Gerontology
    Nihon Rinsho 66:1149-54. 2008
    ..Here we describe recent progress toward understanding the pathogenic role of MuSK antibodies in the decline of muscle strength that typifies MG...
  89. ncbi Aberrant development of motor axons and neuromuscular synapses in MyoD-null mice
    Zuo Zhong Wang
    Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Neurosci 23:5161-9. 2003
    ..However, MyoD-/- mice assemble a complex postsynaptic apparatus that includes muscle-specific kinase (MuSK), rapsyn, erbB, and utrophin...
  90. ncbi What's in the serum of seronegative MG and LEMS?: MuSK et al
    Angela Abicht
    Neurology 59:1672-3. 2002
  91. ncbi Muscle expression of a local Igf-1 isoform protects motor neurons in an ALS mouse model
    Gabriella Dobrowolny
    Department of Histology and Medical Embryology, CE BEMM and Interuniversity Institute of Myology, University of Rome La Sapienza, 14 00161 Rome, Italy
    J Cell Biol 168:193-9. 2005
    ..These studies establish skeletal muscle as a primary target for the dominant action of inherited SOD1 mutation and suggest that muscle fibers provide appropriate factors, such as mIgf-1, for neuron survival...
  92. ncbi [Clinical and electrophysiological peculiarities of seronegative myasthenia]
    N I Shcherbakova
    Zh Nevrol Psikhiatr Im S S Korsakova 108:4-10. 2008
    ..Neurophysiologic examination displayed extra repetitive discharges after the compound motor action potential (R-CMAP) at low-frequency stimulation after acetylcholine esterase inhibitors in 100% cases...
  93. ncbi MuSK-antibody positive myasthenia gravis: clinical and electrodiagnostic patterns
    D E Stickler
    Division of Neurology, Duke University Medical Center, Durham, NC 27710, USA
    Clin Neurophysiol 116:2065-8. 2005
    ....
  94. ncbi Myasthenia gravis and myasthenic syndrome: simulation of twitch strength with or without therapy
    Vladimir Nigrovic
    Department of Anesthesiology, Medical University of Ohio, 3000 Arlington Avenue, Toledo, Ohio 43614 2598, USA
    Muscle Nerve 32:745-50. 2005
    ..These results provide useful quantitative insights into the relationship between acetylcholine receptors or the stimulus-induced release of acetylcholine and muscle function in myasthenia gravis or Lambert-Eaton myasthenic syndrome...
  95. ncbi Major pathogenic effects of anti-MuSK antibodies in myasthenia gravis
    Neli Boneva
    CNRS UMR 8162, IPSC, Universite Paris XI, Hopital Marie Lannelongue, 133 avenue de la Resistance, 92350 Le Plessis Robinson, France
    J Neuroimmunol 177:119-31. 2006
    ..These effects correlated to disease severity and to anti-MuSK Abs titer and vanished following PE. Altogether, these results indicate that anti-MuSK Abs could be pathogenic by contributing to the muscle atrophy in MuSK+ MG patients...
  96. ncbi Identification of developmentally regulated expression of MuSK in astrocytes of the rodent retina
    Tatiana Cheusova
    Institut fur Biochemie, Universitat Erlangen Nurnberg, Erlangen, Germany
    J Neurochem 99:450-7. 2006
    ..In summary, the presence of MuSK on retinal astrocytes suggests a novel role of MuSK signalling pathways in the CNS...
  97. ncbi Delayed synapsing muscles are more severely affected in an experimental model of MuSK-induced myasthenia gravis
    K Xu
    Department of Biology and Biochemistry, University of Houston, Houston, TX 77204 5001, USA
    Neuroscience 143:655-9. 2006
    ..These results suggest a basis for the differential susceptibility of muscles in different classes of myasthenia gravis patients, including patients with autoantibodies against MuSK...
  98. ncbi Long-term effect of intravenous immunoglobulin on anti-MuSK antibody-positive myasthenia gravis
    A Shibata-Hamaguchi
    Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, 13 1 Takara machi, Kanazawa, Ishikawa, Japan
    Acta Neurol Scand 116:406-8. 2007
    ..The outcome of this case suggests that IVIG treatment may be an effective therapeutic option for anti-MuSK antibody-positive MG, with a potentially long-term effect...
  99. ncbi Anti-MuSK-positive myasthenia gravis: neuromuscular transmission failure in facial and limb muscles
    S Kuwabara
    Department of Neurology, Chiba University School of Medicine, Chiba, Japan
    Acta Neurol Scand 115:126-8. 2007
    ..These results suggest that when the diagnosis of anti-MuSK-positive MG is suspected, SFEMG should be performed in most prominently affected muscles...
  100. ncbi Single-fiber electromyography during menstrual exacerbation and ovulatory suppression in MuSK antibody-positive myasthenia gravis
    David E Stickler
    Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29464, USA
    Muscle Nerve 35:808-11. 2007
    ..The potential long-term benefit of ovulatory suppression in MuSK antibody-positive myasthenia gravis is discussed...
  101. ncbi [Adverse effects of therapeutic drugs on neuromuscular junctions]
    Masakatsu Motomura
    Nippon Naika Gakkai Zasshi 96:1604-7. 2007

Research Grants79

  1. Pope-Presynaptic modulation of anticholinesterase toxicity
    Carey N Pope; Fiscal Year: 2010
    ..leading to acetylcholine accumulation at cholinergic synapses, excessive stimulation of cholinergic receptors and signs of acute toxicity (e.g., tremors, excessive secretions, seizures)...
  2. Nicotine Modulation of Parasympathetic Cardiac Neurons
    David Mendelowitz; Fiscal Year: 2009
    ..neurons, these reflex pathways are endogenously and differentially modulated by nicotinic and muscarinic cholinergic receptors, determine where in this reflex pathway this modulation occurs, and finally whether fetal exposure to ..
  3. Drug Discovery for Cognitive Impairment Associated with Drugs of Abuse
    Alvin V Terry; Fiscal Year: 2010
    ..new compounds evoke their pharmacological actions by a unique mechanism: desensitization of nicotinic cholinergic receptors without the antecedent activation...
  4. CHEMOTRANSDUCTION IN THE CAROTID BODY
    Robert Fitzgerald; Fiscal Year: 2001
    ..11.2. ..
  5. MUSCARINIC RECEPTOR SUBTYPES ON CULTURED CELLS
    T Harden; Fiscal Year: 1991
    The proposed existence of subtypes of muscarinic cholinergic receptors (MR) has been based primarily on pharmacological data obtained with a single atypical MR antagonist, pirenzepine...
  6. PRESYNAPTIC MODULATION OF ANTICHOLINESTERASE TOXICITY
    Carey Pope; Fiscal Year: 2000
    ..of acetylcholinesterase, allowing accumulation of acetylcholine and excessive stimulation of postsynaptic cholinergic receptors. Considerable age-related differences in sensitivity to these agents are evident...
  7. CALCIUM SIGNALING BY HIPPOCAMPAL NICOTINIC RECEPTORS
    Sukumar Vijayaraghavan; Fiscal Year: 2000
    ..The temporal patterns of calcium signals generated by the various cholinergic receptors on these neurons and their interactions with other sources contributing to [Ca]i will be examined in ..
  8. Regulation of Keratinocyte Migration by Acetylcholine
    SERGEI GRANDO; Fiscal Year: 2005
    ..Significance: We will show how nAChRs and mAChRs differentially modulate the function and migration of KC in wound healing which will offer novel solutions for management of skin wounds that fail to heal. ..
  9. Epithelial Acetylcholine Oral Biology and Pathology
    SERGEI GRANDO; Fiscal Year: 2007
    ..SIGNIFICANCE: The role of non-neuronal ACh in oral cell biology and pathology will be elucidated, which will help explain some of the mechanisms of deleterious effects of tobacco products in the upper digestive tract. ..
  10. Sentinel cells that report neural and neurovascular signaling
    David Kleinfeld; Fiscal Year: 2007
    ..The assay has wide ranging applications, including, but not limited to research on abused substances. ..
  11. Receptor Selective Spinal Analgesia
    James Eisenach; Fiscal Year: 2010
    ..This grant has in the past examined spinal a2- adrenergic, adenosine, and cholinergic receptors in pain and analgesia, and in the last cycle began the study of spinal prostaglandins, using the ..
  12. Receptor Selective Spinal Analgesia
    James Eisenach; Fiscal Year: 2007
    ..This grant has in the past examined spinal a2- adrenergic, adenosine, and cholinergic receptors in pain and analgesia, and in the last cycle began the study of spinal prostaglandins, using the ..
  13. Nicotine Addiction: ACh Receptors and Secretion
    Aaron Fox; Fiscal Year: 2002
    ..This new aim is extremely exciting to us and is only possible because of the discovery of this remarkable cell line...
  14. Receptor Selective Spinal Analgesia
    James Eisenach; Fiscal Year: 2009
    ..This grant has in the past examined spinal a2- adrenergic, adenosine, and cholinergic receptors in pain and analgesia, and in the last cycle began the study of spinal prostaglandins, using the ..
  15. Chronic Nicotine Effects on Receptor Subtypes
    David Perry; Fiscal Year: 2009
    The CNS effects of nicotine are mediated by multiple subtypes of neuronal nicotinic cholinergic receptors (nAChRs)...
  16. Chronic Nicotine Effects on Receptor Subtypes
    David C Perry; Fiscal Year: 2010
    The CNS effects of nicotine are mediated by multiple subtypes of neuronal nicotinic cholinergic receptors (nAChRs)...
  17. PRESYNAPTIC MECHANISMS IN THE INTESTINE
    James Galligan; Fiscal Year: 2003
    ..These studies will investigate the contributions of acetylcholine (ACh) acting at nicotinic cholinergic receptors and ATP acting at P2X purine receptors, to fast excitatory synaptic potentials (fEPSPs) during long trains ..