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Postsynaptic Membranes at the Neuromuscular Junction: Molecular Organisation

  1. Jean Cartaud1,
  2. Ekaterini Kordeli2,
  3. Annie Cartaud1

Published Online: 19 APR 2010

DOI: 10.1002/9780470015902.a0000252.pub2

eLS

eLS

How to Cite

Cartaud, J., Kordeli, E. and Cartaud, A. 2010. Postsynaptic Membranes at the Neuromuscular Junction: Molecular Organisation. eLS. .

Author Information

  1. 1

    CNRS & Université Paris-Diderot, Institut Jacques Monod, Paris, France

  2. 2

    INSERM & Institut National de la Transfusion Sanguine, Paris, France

Publication History

  1. Published Online: 19 APR 2010

Abstract

Accurate neurotransmission between motor nerve and muscle fibres at the vertebrate cholinergic neuromuscular junction (NMJ) depends on the differentiation of highly specialised structures both pre- and postsynaptically. The accumulation of nicotinic acetylcholine receptors (AChRs) and voltage-gated sodium channels represents the hallmark of postsynaptic membrane differentiation. Several synaptic organising proteins are required for the aggregation of postsynaptic AChRs. The muscle-specific receptor tyrosine kinase (MuSK) provides a structural scaffold necessary to initiate aggregates of postsynaptic molecules. Agrin – a nerve-derived extracellular matrix glycoprotein – is required for AChR clustering probably by activating MuSK activity. Rapsyn – the AChR-associated peripheral protein acting downstream of agrin–MuSK signalling – is essential for AChR clustering. These proteins, together with a wealth of other components of the synapse, cooperate in multiple ways to play both structural and signalling roles in synaptic differentiation. Synaptopathies of the NMJ result from mutations in several key players of synaptic differentiation.

Key Concepts:

  • Efficient communication between neurons or between neurons and their targets requires the enrichment of synaptic proteins, in particular, ligand-gated ion channels at postsynaptic sites.

  • The NMJ represents a particularly striking example of accumulation of nicotinic acetylcholine receptors in the postsynaptic membrane and is an ideal model to study receptor clustering.

  • Formation and maintenance of the postsynaptic membrane is a complex mechanism involving synaptic organising molecules derived both from nerve and muscle.

  • The muscle tyrosine kinase, MuSK, is the master organiser of the NMJ capable to initiate clustering of postsynaptic components, even in the absence of neuronal cues.

  • Mutations in several components of the postsynaptic membrane (not only in AChR subunits genes but also in agrin, ColQ, DOK-7, laminin, MuSK, rapsyn, etc.) result in severe dysfunction of the NMJ: the congenital myasthenic syndromes.

Keywords:

  • acetylcholinesterase;
  • agrin;
  • congenital myasthenic syndromes;
  • nicotinic acetylcholine receptor;
  • voltage-sensitive sodium channel;
  • rapsyn;
  • synapse