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| cholinergic receptorsSummarySummary: 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
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The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivoT M DeChiara
Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591, USA
Cell 85:501-12. 1996....
Distinct domains of MuSK mediate its abilities to induce and to associate with postsynaptic specializationsH 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...
Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophyA 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...
LRP4 serves as a coreceptor of agrinBin 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...
MuSK controls where motor axons grow and form synapsesNatalie 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....
Acetylcholine receptors loss and postsynaptic damage in MuSK antibody-positive myasthenia gravisHirokazu 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...
The role of nerve- versus muscle-derived factors in mammalian neuromuscular junction formationShuo 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...
Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravisAmelia Evoli
Department of Neuroscience, Catholic University, Roma, Italy
Brain 126:2304-11. 2003....
Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxinL 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...
The in vitro and in vivo phosphotyrosine map of activated MuSKA 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...
Chronic aspartame affects T-maze performance, brain cholinergic receptors and Na+,K+-ATPase in ratsBrandon 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 ..
Impaired synaptic vesicle release and immaturity of neuromuscular junctions in spinal muscular atrophy miceLingling 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...
Postsynaptic abnormalities at the neuromuscular junctions of utrophin-deficient miceA 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...
Tyrosine-phosphorylated and nonphosphorylated isoforms of alpha-dystrobrevin: roles in skeletal muscle and its neuromuscular and myotendinous junctionsR 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...
Agrin-induced phosphorylation of the acetylcholine receptor regulates cytoskeletal anchoring and clusteringL S Borges
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3A 2T5, Canada
J Cell Biol 153:1-12. 2001....
A mammalian homolog of Drosophila tumorous imaginal discs, Tid1, mediates agrin signaling at the neuromuscular junctionJenny 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...
Assembly of the postsynaptic membrane at the neuromuscular junction: paradigm lostTerrance 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...
Impaired off-line consolidation of motor memories after combined blockade of cholinergic receptors during REM sleep-rich sleepBjörn 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...
Identification of an element crucial for the sub-synaptic expression of the acetylcholine receptor epsilon-subunit geneA 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...
Lithocholyltaurine interacts with cholinergic receptors on dispersed chief cells from guinea pig stomachJ 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.
Induction of multiple signaling loops by MuSK during neuromuscular synapse formationC 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...
Combined blockade of cholinergic receptors shifts the brain from stimulus encoding to memory consolidationBjörn H Rasch
University of Lubeck, Germany
J Cogn Neurosci 18:793-802. 2006....
Expression of mutant Ets protein at the neuromuscular synapse causes alterations in morphology and gene expressionAlban 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...
The Agrin/MuSK signaling pathway is spatially segregated from the neuregulin/ErbB receptor signaling pathway at the neuromuscular junctionJ 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...
Acetylcholine receptor clustering and triton solubility: neural effectT R Podleski
Section of Neurobiology and Behavior, Cornell University, Ithaca, New York 14853
J Neurobiol 19:167-85. 1988....
Zebrafish unplugged reveals a role for muscle-specific kinase homologs in axonal pathway choiceJing 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...
Laminin and alpha7beta1 integrin regulate agrin-induced clustering of acetylcholine receptorsD J Burkin
Department of Cell and Structural Biology, University of Illinois, Urbana, IL 61801, USA
J Cell Sci 113:2877-86. 2000....
Maintenance of acetylcholine receptor number by neuregulins at the neuromuscular junction in vivoA 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...
Pre- and postsynaptic maturation of the neuromuscular junction during neonatal synapse elimination depends on protein kinase CMaria 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...
The role of the dorsal raphe-serotonergic system and cholinergic receptors in the modulation of working memoryS 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 ..
Morphine-induced place preference: involvement of cholinergic receptors of the ventral tegmental areaAmeneh 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...
Rescue of the cardiac defect in ErbB2 mutant mice reveals essential roles of ErbB2 in peripheral nervous system developmentJ 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...
The expression and biological role of the non-neuronal cholinergic system in the ovaryArtur 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...
MuSK induces in vivo acetylcholine receptor clusters in a ligand-independent mannerA 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...
Interaction of chlorphenvinphos with cholinergic receptors in the rabbit hypothalamusS 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...
Development of the neuromuscular junctionVeit Witzemann
Max Planck Institut fur medizinische Forschung, Jahnstrasse 29, 69120 Heidelberg, Germany
Cell Tissue Res 326:263-71. 2006....
Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapseW 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...
Agrin acts via a MuSK receptor complexD 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...
Aberrant patterning of neuromuscular synapses in choline acetyltransferase-deficient miceEugene 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...
Neuromuscular synapses can form in vivo by incorporation of initially aneural postsynaptic specializationsHeather 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...
The relationship between perlecan and dystroglycan and its implication in the formation of the neuromuscular junctionH 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...
Blockade of central cholinergic receptors impairs new learning and increases proactive interference in a word paired-associate memory taskAlireza Atri
Boston University, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02215, USA
Behav Neurosci 118:223-36. 2004Experimental 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...
Gating of acetylcholine receptor channels: brownian motion across a broad transition stateAnthony 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...
Congenital myasthenic syndromes and the formation of the neuromuscular junctionDavid Beeson
Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
Ann N Y Acad Sci 1132:99-103. 2008....
Nerve terminals form but fail to mature when postsynaptic differentiation is blocked: in vivo analysis using mammalian nerve-muscle chimerasQ 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...
Syne-1, a dystrophin- and Klarsicht-related protein associated with synaptic nuclei at the neuromuscular junctionE 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...
AChR phosphorylation and indirect inhibition of AChR function in seronegative MGC 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...
Neurotransmitter acetylcholine negatively regulates neuromuscular synapse formation by a Cdk5-dependent mechanismWeichun 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...
Dynamics of the acetylcholine receptor pore at the gating transition stateAnanya 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....
Crystal structure of the MuSK tyrosine kinase: insights into receptor autoregulationJeffrey 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...
Unravelling the pathogenesis of myasthenia gravisAngela 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....
Neuromuscular synaptogenesis: clustering of acetylcholine receptors revisitedR Willmann
Department of Neurochemistry, Brain Research Institute, , Switzerland
Cell Mol Life Sci 59:1296-316. 2002....
Synapse disassembly and formation of new synapses in postnatal muscle upon conditional inactivation of MuSKBoris 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...
Seronegative myasthenia gravis: disease severity and prognosisF 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...
Initial phase 2 trial of a nicotinic agonist in schizophreniaRobert 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...
Tyrosine phosphatase regulation of MuSK-dependent acetylcholine receptor clusteringRaghavan 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...
The dystroglycan complex is necessary for stabilization of acetylcholine receptor clusters at neuromuscular junctions and formation of the synaptic basement membraneC 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...
In vivo imaging of preferential motor axon outgrowth to and synaptogenesis at prepatterned acetylcholine receptor clusters in embryonic zebrafish skeletal muscleJessica 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...
Molecular regulation of postsynaptic differentiation at the neuromuscular junctionRaghavan 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...
DNA topoisomerase IIbeta and neural developmentX 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...
Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal gamma subunitKatrin Hoffmann
Institute of Medical Genetics, Charite University Medical School, Humboldt University, 13353 Berlin, Germany
Am J Hum Genet 79:303-12. 2006....
Differential involvement of M1-type and M4-type muscarinic cholinergic receptors in the dorsomedial striatum in task switchingMartha 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...
The role of loop 5 in acetylcholine receptor channel gatingSudha 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...
Inhibition of synapse assembly in mammalian muscle in vivo by RNA interferenceXian 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...
A quantitative fluorescence-imaging technique for studying acetylcholine receptor turnover at neuromuscular junctions in living animalsS G Turney
Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO 63110, USA
J Neurosci Methods 64:199-208. 1996....
Detection and characterization of MuSK antibodies in seronegative myasthenia gravisJohn 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...
An amino-terminal extension is required for the secretion of chick agrin and its binding to extracellular matrixA 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...
Laminin and alpha-dystroglycan mediate acetylcholine receptor aggregation via a MuSK-independent pathwayF 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...
Structure and gating mechanism of the acetylcholine receptor poreAtsuo 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...
Localization and regulation of MuSK at the neuromuscular junctionD 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...
Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophreniaAnantha 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...
Cholinergic systems in progressive supranuclear palsyN 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...
Rapid and reversible effects of activity on acetylcholine receptor density at the neuromuscular junction in vivoM 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...
Formation of the neuromuscular junction. Agrin and its unusual receptorsW 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...
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....
Acetylcholine receptor gating at extracellular transmembrane domain interface: the cys-loop and M2-M3 linkerArchana 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...
Muscle-wide secretion of a miniaturized form of neural agrin rescues focal neuromuscular innervation in agrin mutant miceShuo 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...
ATP potentiates agrin-induced AChR aggregation in cultured myotubes: activation of RhoA in P2Y1 nucleotide receptor signaling at vertebrate neuromuscular junctionsKaren 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....
Microcontact printing: a versatile technique for the study of synaptogenic moleculesToby 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...
Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1Zhen 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...
A novel pathway for MuSK to induce key genes in neuromuscular synapse formationEric 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...
The features of myasthenia gravis with autoantibodies to MuSKD 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...
Autoimmune myasthenia gravis in childhoodP 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...
Regulation of acetylcholine receptor clustering by the tumor suppressor APCJunmei 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...
Seronegative myasthenia gravisAngela 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...
Effect of D-penicillamine on neuromuscular junction in patients with Wilson diseaseR N Komal Kumar
Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
Neurology 63:935-6. 2004
Molecular dissection of neuromuscular junction formationWerner 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...
[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...
Aberrant development of motor axons and neuromuscular synapses in MyoD-null miceZuo 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...
What's in the serum of seronegative MG and LEMS?: MuSK et alAngela Abicht
Neurology 59:1672-3. 2002
Muscle expression of a local Igf-1 isoform protects motor neurons in an ALS mouse modelGabriella 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...
[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...
MuSK-antibody positive myasthenia gravis: clinical and electrodiagnostic patternsD E Stickler
Division of Neurology, Duke University Medical Center, Durham, NC 27710, USA
Clin Neurophysiol 116:2065-8. 2005....
Myasthenia gravis and myasthenic syndrome: simulation of twitch strength with or without therapyVladimir 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...
Major pathogenic effects of anti-MuSK antibodies in myasthenia gravisNeli 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...
Identification of developmentally regulated expression of MuSK in astrocytes of the rodent retinaTatiana 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...
Delayed synapsing muscles are more severely affected in an experimental model of MuSK-induced myasthenia gravisK 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...
Long-term effect of intravenous immunoglobulin on anti-MuSK antibody-positive myasthenia gravisA 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...
Anti-MuSK-positive myasthenia gravis: neuromuscular transmission failure in facial and limb musclesS 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...
Single-fiber electromyography during menstrual exacerbation and ovulatory suppression in MuSK antibody-positive myasthenia gravisDavid 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...
[Adverse effects of therapeutic drugs on neuromuscular junctions]Masakatsu Motomura
Nippon Naika Gakkai Zasshi 96:1604-7. 2007
Research Grants
- Pope-Presynaptic modulation of anticholinesterase toxicityCarey 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)...
- Nicotine Modulation of Parasympathetic Cardiac NeuronsDavid 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 ..
- Drug Discovery for Cognitive Impairment Associated with Drugs of AbuseAlvin V Terry; Fiscal Year: 2010..new compounds evoke their pharmacological actions by a unique mechanism: desensitization of nicotinic cholinergic receptors without the antecedent activation...
- CHEMOTRANSDUCTION IN THE CAROTID BODYRobert Fitzgerald; Fiscal Year: 2001..11.2. ..
- MUSCARINIC RECEPTOR SUBTYPES ON CULTURED CELLST Harden; Fiscal Year: 1991The proposed existence of subtypes of muscarinic cholinergic receptors (MR) has been based primarily on pharmacological data obtained with a single atypical MR antagonist, pirenzepine...
- PRESYNAPTIC MODULATION OF ANTICHOLINESTERASE TOXICITYCarey 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...
- CALCIUM SIGNALING BY HIPPOCAMPAL NICOTINIC RECEPTORSSukumar 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 ..
- Regulation of Keratinocyte Migration by AcetylcholineSERGEI 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. ..
- Epithelial Acetylcholine Oral Biology and PathologySERGEI 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. ..
- Sentinel cells that report neural and neurovascular signalingDavid Kleinfeld; Fiscal Year: 2007..The assay has wide ranging applications, including, but not limited to research on abused substances. ..
- Receptor Selective Spinal AnalgesiaJames 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 ..
- Receptor Selective Spinal AnalgesiaJames 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 ..
- Nicotine Addiction: ACh Receptors and SecretionAaron 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...
- Receptor Selective Spinal AnalgesiaJames 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 ..
- Chronic Nicotine Effects on Receptor SubtypesDavid Perry; Fiscal Year: 2009The CNS effects of nicotine are mediated by multiple subtypes of neuronal nicotinic cholinergic receptors (nAChRs)...
- Chronic Nicotine Effects on Receptor SubtypesDavid C Perry; Fiscal Year: 2010The CNS effects of nicotine are mediated by multiple subtypes of neuronal nicotinic cholinergic receptors (nAChRs)...
- PRESYNAPTIC MECHANISMS IN THE INTESTINEJames 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 ..
