Molecular regulation of postsynaptic differentiation at the neuromuscular junction.
The neuromuscular junction (NMJ) is a synapse that develops between a motor neuron and a muscle fiber. A defining feature of NMJ development in vertebrates is the re-distribution of muscle acetylcholine (ACh) receptors (AChRs) following innervation, which generates high-density AChR clusters at the postsynaptic membrane and disperses aneural AChR clusters formed in muscle before innervation. This process in vivo requires MuSK, a muscle-specific receptor tyrosine kinase that triggers AChR re-distribution when activated; rapsyn, a muscle protein that binds and clusters AChRs; agrin, a nerve-secreted heparan-sulfate proteoglycan that activates MuSK; and ACh, a neurotransmitter that stimulates muscle and also disperses aneural AChR clusters. Moreover, in cultured muscle cells, several additional muscle- and nerve-derived molecules induce, mediate or participate in AChR clustering and dispersal. In this review we discuss how regulation of AChR re-distribution by multiple factors ensures aggregation of AChRs exclusively at NMJs.
Madhavan
Raghavan
R
Department of Biology, Hong Kong University of Science and Technology, Kowloon, Hong Kong, China.
Peng
H Benjamin
HB
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D006801:Humans; D009469:Neuromuscular Junction / Q000166:cytology / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism*
D011950:Receptors, Cholinergic