Genomes and Genes
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.
- Chevessier F, Girard E, Molgo J, Bartling S, Koenig J, Hantai D, et al. A mouse model for congenital myasthenic syndrome due to MuSK mutations reveals defects in structure and function of neuromuscular junctions. Hum Mol Genet. 2008;17:3577-95 pubmed publisher..These mutant mice represent valuable models for elucidating the roles of MuSK for synapse formation, maturation and maintenance as well as for studying the pathophysiology of a CMS due to MuSK mutations...
- Chan K, LaChance D, Harper C, Lennon V. Frequency of seronegativity in adult-acquired generalized myasthenia gravis. Muscle Nerve. 2007;36:651-8 pubmed..Classification as seronegative MG should be reserved for nonimmunosuppressed patients with generalized MG who lack muscle AChR binding, AChR modulating, or MuSK antibodies at presentation and at follow-up of at least 12 months. ..
- Rasch B, Gais S, Born J. Impaired off-line consolidation of motor memories after combined blockade of cholinergic receptors during REM sleep-rich sleep. Neuropsychopharmacology. 2009;34:1843-53 pubmed publisher..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. ..
- Geng L, Zhang H, Peng H. The formation of acetylcholine receptor clusters visualized with quantum dots. BMC Neurosci. 2009;10:80 pubmed publisher..This study also provides a clearer picture of the "trap" that it is not a uniformly sticky area but consists of discrete foci at which AChRs are immobilized. ..
- Kong L, Wang X, Choe D, Polley M, Burnett B, Bosch Marce M, et al. Impaired synaptic vesicle release and immaturity of neuromuscular junctions in spinal muscular atrophy mice. J Neurosci. 2009;29:842-51 pubmed publisher..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. ..
- Kim N, Burden S. MuSK controls where motor axons grow and form synapses. Nat Neurosci. 2008;11:19-27 pubmed
- Makara J, Katona I, Nyiri G, Németh B, Ledent C, Watanabe M, et al. Involvement of nitric oxide in depolarization-induced suppression of inhibition in hippocampal pyramidal cells during activation of cholinergic receptors. J Neurosci. 2007;27:10211-22 pubmed..Here we show that, during activation of cholinergic receptors, retrograde signaling by NO controls CB1 cannabinoid receptor (CB1R)-dependent depolarization-induced ..
- Huze C, Bauché S, Richard P, Chevessier F, Goillot E, Gaudon K, et al. Identification of an agrin mutation that causes congenital myasthenia and affects synapse function. Am J Hum Genet. 2009;85:155-67 pubmed publisher..These results indicate that the mutation does not interfere with the ability of agrin to induce postsynaptic structures but that it dramatically perturbs the maintenance of the neuromuscular junction...
- Zhao X, Qian Y, Chan A, Madhavan R, Peng H. Regulation of ACh receptor clustering by the tyrosine phosphatase Shp2. Dev Neurobiol. 2007;67:1789-801 pubmed..We propose that an inhibitory loop involving both tyrosine kinases and phosphatases sets the level of agrin/MuSK signaling and constrains it spatially to help generate high-density AChR clusters selectively at NMJs. ..
- Panzer J, Song Y, Balice Gordon R. In vivo imaging of preferential motor axon outgrowth to and synaptogenesis at prepatterned acetylcholine receptor clusters in embryonic zebrafish skeletal muscle. J Neurosci. 2006;26:934-47 pubmed..Thus, during initial synaptogenesis, postsynaptic differentiation precedes presynaptic differentiation, and prepatterned neurotransmitter clusters mark sites destined for synapse formation. ..
- Pavlov V, Tracey K. Controlling inflammation: the cholinergic anti-inflammatory pathway. Biochem Soc Trans. 2006;34:1037-40 pubmed
- Rasch B, Born J, Gais S. Combined blockade of cholinergic receptors shifts the brain from stimulus encoding to memory consolidation. J Cogn Neurosci. 2006;18:793-802 pubmed
- Okada K, Inoue A, Okada M, Murata Y, Kakuta S, Jigami T, et al. The muscle protein Dok-7 is essential for neuromuscular synaptogenesis. Science. 2006;312:1802-5 pubmed publisher..Mice lacking Dok-7 formed neither acetylcholine receptor clusters nor neuromuscular synapses. Thus, Dok-7 is essential for neuromuscular synaptogenesis through its interaction with MuSK...
- Milholland R, Dulla C, Gordon H. L-type calcium channels mediate acetylcholine receptor aggregation on cultured muscle. Dev Neurobiol. 2007;67:987-98 pubmed..Our results establish a novel role for L-CaChs as important sources of the intracellular calcium necessary for the aggregation of AChRs. ..
- Rezayof A, Nazari Serenjeh F, Zarrindast M, Sepehri H, Delphi L. Morphine-induced place preference: involvement of cholinergic receptors of the ventral tegmental area. Eur J Pharmacol. 2007;562:92-102 pubmed..We conclude that muscarinic and nicotinic acetylcholine receptors in the ventral tegmental area may critically mediate the rewarding effects of morphine. ..
- Kummer T, Misgeld T, Sanes J. Assembly of the postsynaptic membrane at the neuromuscular junction: paradigm lost. Curr Opin Neurobiol. 2006;16:74-82 pubmed..These recent studies challenge the widely-held paradigms, although not the results that led to them, and suggest a new model for neuromuscular synaptogenesis. ..
- Madhavan R, Peng H. Molecular regulation of postsynaptic differentiation at the neuromuscular junction. IUBMB Life. 2005;57:719-30 pubmed..In this review we discuss how regulation of AChR re-distribution by multiple factors ensures aggregation of AChRs exclusively at NMJs. ..
- Morgan N, Brueton L, Cox P, Greally M, Tolmie J, Pasha S, et al. Mutations in the embryonal subunit of the acetylcholine receptor (CHRNG) cause lethal and Escobar variants of multiple pterygium syndrome. Am J Hum Genet. 2006;79:390-5 pubmed..These findings extend the role of acetylcholine receptor dysfunction in human disease and provide new insights into the pathogenesis and management of fetal akinesia syndromes. ..
- Beeson D, Higuchi O, Palace J, Cossins J, Spearman H, Maxwell S, et al. Dok-7 mutations underlie a neuromuscular junction synaptopathy. Science. 2006;313:1975-8 pubmed..We showed that recessive inheritance of mutations in Dok-7, which result in a defective structure of the neuromuscular junction, is a cause of CMS with proximal muscle weakness...
- Camilleri A, Willmann R, Sadasivam G, Lin S, Ruegg M, Gesemann M, et al. Tyrosine phosphatases such as SHP-2 act in a balance with Src-family kinases in stabilization of postsynaptic clusters of acetylcholine receptors. BMC Neurosci. 2007;8:46 pubmed..One phosphatase that acts in this equilibrium is SHP-2. Thus, PTPs such as SHP-2 stabilize AChR clusters under normal circumstances, but when these PTPs are not balanced by SFKs, they render clusters unstable. ..
- Witzemann V. Development of the neuromuscular junction. Cell Tissue Res. 2006;326:263-71 pubmed
- Dong X, Li X, Gao T, Zhang E, Feng G, Xiong W, et al. Shp2 is dispensable in the formation and maintenance of the neuromuscular junction. Neurosignals. 2006;15:53-63 pubmed..Both the frequency and amplitude of mEPPs in CKO mice were similar to those in controls, suggesting normal neurotransmission when SHP2 was deficient. These results suggest that Shp2 is not required for NMJ formation and/or maintenance. ..
- Willmann R, Pun S, Stallmach L, Sadasivam G, Santos A, Caroni P, et al. Cholesterol and lipid microdomains stabilize the postsynapse at the neuromuscular junction. EMBO J. 2006;25:4050-60 pubmed
- Madhavan R, Zhao X, Reynolds A, Peng H. Involvement of p120 catenin in myopodial assembly and nerve-muscle synapse formation. J Neurobiol. 2006;66:1511-27 pubmed..Our results indicate a novel role of p120ctn in agrin-induced myopodial assembly and suggest that myopodia increase muscle-nerve contacts and muscle's access to neural agrin to promote NMJ formation. ..
- Ngo S, Noakes P, Phillips W. Neural agrin: a synaptic stabiliser. Int J Biochem Cell Biol. 2007;39:863-7 pubmed..Here we briefly review some key mechanisms through which neural agrin acts to foster the formation of mature neuromuscular synapses. ..
- Milholland R, Gordon H. A role for acetylcholine receptors in their own aggregation on muscle cells. Dev Neurobiol. 2007;67:999-1008 pubmed..The AChR/L-CaCh pathway provides a mechanism by which neuromuscular signal transmission can act in concert with the agrin-MuSK signaling cascade to regulate NMJ formation. ..
- Hoffmann K, Muller J, Stricker S, Megarbane A, Rajab A, Lindner T, et al. Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal gamma subunit. Am J Hum Genet. 2006;79:303-12 pubmed
- Stetzkowski Marden F, Gaus K, Recouvreur M, Cartaud A, Cartaud J. Agrin elicits membrane lipid condensation at sites of acetylcholine receptor clusters in C2C12 myotubes. J Lipid Res. 2006;47:2121-33 pubmed..These data led us to propose a model in which lipid rafts play a pivotal role in the assembly of the postsynaptic membrane at the neuromuscular junction upon agrin signaling. ..
- Chen F, Qian L, Yang Z, Huang Y, Ngo S, Ruan N, et al. Rapsyn interaction with calpain stabilizes AChR clusters at the neuromuscular junction. Neuron. 2007;55:247-60 pubmed..These results demonstrate that calpain participates in ACh-induced dispersion of AChR clusters, and rapsyn stabilizes AChR clusters by suppressing calpain activity. ..
- Sadasivam G, Willmann R, Lin S, Erb Vögtli S, Kong X, Ruegg M, et al. Src-family kinases stabilize the neuromuscular synapse in vivo via protein interactions, phosphorylation, and cytoskeletal linkage of acetylcholine receptors. J Neurosci. 2005;25:10479-93 pubmed..SFKs hold the postsynaptic apparatus together through stabilization of AChR-rapsyn interaction and AChR phosphorylation. In addition, SFKs control rapsyn levels and AChR-cytoskeletal linkage. ..
- Cossins J, Burke G, Maxwell S, Spearman H, Man S, Kuks J, et al. Diverse molecular mechanisms involved in AChR deficiency due to rapsyn mutations. Brain. 2006;129:2773-83 pubmed..The disease severity of patients harbouring the compound allelic mutations was greater than that of patients with homozygous rapsyn mutation N88K, suggesting that the second mutant allele may largely determine severity...
- Slater C, Fawcett P, Walls T, Lyons P, Bailey S, Beeson D, et al. Pre- and post-synaptic abnormalities associated with impaired neuromuscular transmission in a group of patients with 'limb-girdle myasthenia'. Brain. 2006;129:2061-76 pubmed
- Bschleipfer T, Schukowski K, Weidner W, Grando S, Schwantes U, Kummer W, et al. Expression and distribution of cholinergic receptors in the human urothelium. Life Sci. 2007;80:2303-7 pubmed..In view of the multiplicity of pathways to which different cholinergic receptor subtypes are coupled, we propose that this layer-specific distribution serves to stratify cholinergic regulation of human urothelial function. ..
- Nizhynska V, Neumueller R, Herbst R. Phosphoinositide 3-kinase acts through RAC and Cdc42 during agrin-induced acetylcholine receptor clustering. Dev Neurobiol. 2007;67:1047-58 pubmed..Its role during agrin-stimulated Rac and Cdc42 activation suggests a critical function during cytoskeletal reorganizations, which lead to the redistribution of actin-anchored AChRs. ..
- Hesser B, Henschel O, Witzemann V. Synapse disassembly and formation of new synapses in postnatal muscle upon conditional inactivation of MuSK. Mol Cell Neurosci. 2006;31:470-80 pubmed..Thus, MuSK and AChR together maintain the functional and structural integrity of the postsynaptic architecture and prevent axon growth. ..
- Purohit P, Mitra A, Auerbach A. A stepwise mechanism for acetylcholine receptor channel gating. Nature. 2007;446:930-3 pubmed..The core of the channel serves both as a gate that regulates ion flow and as a hub that directs the propagation of the gating isomerization through the membrane domain of the acetylcholine receptor. ..
- Weston C, Teressa G, Weeks B, Prives J. Agrin and laminin induce acetylcholine receptor clustering by convergent, Rho GTPase-dependent signaling pathways. J Cell Sci. 2007;120:868-75 pubmed..Therefore, although agrin and laminin use distinct transmembrane receptors to initiate AChR clustering, their signaling pathways converge at the level of Rho GTPase activation. ..
- Cymes G, Ni Y, Grosman C. Probing ion-channel pores one proton at a time. Nature. 2005;438:975-80 pubmed..A comparison with closed-channel data leads us to propose that the rotation of M2, which is frequently invoked as a hallmark of the gating mechanism of Cys-loop receptors, is minimal, if any. ..
- Farrugia M, Bonifati D, Clover L, Cossins J, Beeson D, Vincent A. Effect of sera from AChR-antibody negative myasthenia gravis patients on AChR and MuSK in cell cultures. J Neuroimmunol. 2007;185:136-44 pubmed..Thus, although these results have, disappointingly, demonstrated little effect of MuSK antibodies on AChR expression, they do imply that SNMG antibodies act on AChR-associated pathways. ..
- Cole R, Reddel S, Gervasio O, Phillips W. Anti-MuSK patient antibodies disrupt the mouse neuromuscular junction. Ann Neurol. 2008;63:782-9 pubmed publisher..This may be explained by a progressive reduction in the density of postsynaptic AChR combined with changes in the nerve terminal and its relation to the postsynaptic structure. ..
- Bafna P, Purohit P, Auerbach A. Gating at the mouth of the acetylcholine receptor channel: energetic consequences of mutations in the alphaM2-cap. PLoS ONE. 2008;3:e2515 pubmed publisher..The results suggest that the alphaM2-cap changes its secondary structure to link gating motions in the extracellular domain with those in the channel that regulate ionic conductance. ..
- Miike T, Kunishiro K, Kanda M, Azukizawa S, Kurahashi K, Shirahase H. Impairment of endothelium-dependent ACh-induced relaxation in aorta of diabetic db/db mice--possible dysfunction of receptor and/or receptor-G protein coupling. Naunyn Schmiedebergs Arch Pharmacol. 2008;377:401-10 pubmed publisher..Endothelial dysfunction was not genetic and was considered to be initiated primarily by hyperglycemia, and was improved by anti-diabetic treatment with a PPARgamma agonist. ..
- Spengos K, Vassilopoulou S, Papadimas G, Tsivgoulis G, Karandreas N, Zambelis T, et al. Dropped head syndrome as prominent clinical feature in MuSK-positive Myasthenia Gravis with thymus hyperplasia. Neuromuscul Disord. 2008;18:175-7 pubmed
- Grueter B, McElligott Z, Winder D. Group I mGluRs and long-term depression: potential roles in addiction?. Mol Neurobiol. 2007;36:232-44 pubmed..In this review, we focus first on the evidence supporting a role for mGluRs in addiction and then on the properties of mGluR-dependent forms of synaptic plasticity, focusing in particular on Gq-linked receptor-induced LTD. ..
- Callaghan B, Moster M, Bird S. Myasthenia gravis with presynaptic electrophysiologic abnormalities. J Clin Neuromuscul Dis. 2009;10:185-90 pubmed publisher..This may occur even in the absence of the typical clinical and serologic features of the Lambert-Eaton syndrome. It is possible that there is another antibody present that is modulating presynaptic acetylcholine release. ..
- Zhang Y, Liu A, Zhang W, Jiang H, Cai Z. Correlation of contractile function recovery with acetylcholine receptor changes in a rat muscle flap model. Microsurgery. 2010;30:307-13 pubmed publisher..Our findings may provide evidence for further study of improving muscle function in functional reconstruction by targeting the AChR. ..
- Zagar M, Vranjes D, Sostarko M, Vogrinc Z, Bilic E, Trbojević Cepe M. Myasthenia gravis patients with anti-MuSK antibodies. Coll Antropol. 2009;33:1151-4 pubmed..All anti-MuSK positive patients were treated with immunosuppressive drugs, three received plasmapheresis and one patient required mechanical ventilation. Our results are consistent with other literature reports. ..
- Kakino M, Izuta H, Ito T, Tsuruma K, Araki Y, Shimazawa M, et al. Agarwood induced laxative effects via acetylcholine receptors on loperamide-induced constipation in mice. Biosci Biotechnol Biochem. 2010;74:1550-5 pubmed..These findings indicate that EEAs exerted a laxative effect via acetylcholine receptors in the mouse constipation model...
- Blanco Hernández T, Navarré Gimeno A, Brocalero Camacho A, Cervelló Donderis A, Lopez Trigo J, Ortiz Sánchez P, et al. [Methods for diagnosing seronegative myasthenia gravis]. Rev Neurol. 2008;46:360-4 pubmed