Clustering of nicotinic acetylcholine receptors: from the neuromuscular junction to interneuronal synapses.
Fast and accurate synaptic transmission requires high-density accumulation of neurotransmitter receptors in the postsynaptic membrane. During development of the neuromuscular junction, clustering of acetylcholine receptors (AChR) is one of the first signs of postsynaptic specialization and is induced by nerve-released agrin. Recent studies have revealed that different mechanisms regulate assembly vs stabilization of AChR clusters and of the postsynaptic apparatus. MuSK, a receptor tyrosine kinase and component of the agrin receptor, and rapsyn, an AChR-associated anchoring protein, play crucial roles in the postsynaptic assembly. Once formed, AChR clusters and the postsynaptic membrane are stabilized by components of the dystrophin/utrophin glycoprotein complex, some of which also direct aspects of synaptic maturation such as formation of postjunctional folds. Nicotinic receptors are also expressed across the peripheral and central nervous system (PNS/CNS). These receptors are localized not only at the pre- but also at the postsynaptic sites where they carry out major synaptic transmission. In neurons, they are found as clusters at synaptic or extrasynaptic sites, suggesting that different mechanisms might underlie this specific localization of nicotinic receptors. This review summarizes the current knowledge about formation and stabilization of the postsynaptic apparatus at the neuromuscular junction and extends this to explore the synaptic structures of interneuronal cholinergic synapses.
Huh
Kyung-Hye
KH
Department of Neurochemistry, Brain Research Institute, University of Zürich, Switzerland.
Fuhrer
Christian
C
D018171:Agrin / Q000378:metabolism; D000818:Animals; D002799:Cholinergic Fibers / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000502:physiology; D016189:Dystrophin / Q000502:physiology; D006801:Humans; D007395:Interneurons; D007797:Laminin / Q000502:physiology; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008818:Mice, Neurologic Mutants; D008959:Models, Neurological; D009124:Muscle Proteins / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D009469:Neuromuscular Junction / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000502:physiology; D009844:Oligosaccharides / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D011950:Receptors, Cholinergic / Q000502:physiology; D017978:Receptors, Growth Factor / Q000502:physiology; D011978:Receptors, Nicotinic / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission; D049411:Utrophin; D019061:src-Family Kinases / Q000502:physiology
D018171:Agrin; D003598:Cytoskeletal Proteins; D016189:Dystrophin; D007797:Laminin; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D009844:Oligosaccharides; D011950:Receptors, Cholinergic; D017978:Receptors, Growth Factor; D011978:Receptors, Nicotinic; C483600:Utrn protein, mouse; D049411:Utrophin; C080030:agrin receptor; C051609:peripheral membrane protein 43K; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D019061:src-Family Kinases