Muscle Specific Kinase: Organiser of synaptic membrane domains

Nazanin Ghazanfari, Kristine J. Fernandez, Yui Murata, Marco Morsch, Shyuan T. Ngo, Stephen W. Reddel, Peter G. Noakes, William D. Phillips

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

Muscle Specific Kinase (MuSK) is a transmembrane tyrosine kinase vital for forming and maintaining the mammalian neuromuscular junction (NMJ: the synapse between motor nerve and skeletal muscle). MuSK expression switches on during skeletal muscle differentiation. MuSK then becomes restricted to the postsynaptic membrane of the NMJ, where it functions to cluster acetylcholine receptors (AChRs). The expression, activation and turnover of MuSK are each regulated by signals from the motor nerve terminal. MuSK forms the core of an emerging signalling complex that can be acutely activated by neural agrin (N-agrin), a heparin sulfate proteoglycan secreted from the nerve terminal. MuSK activation initiates complex intracellular signalling events that coordinate the local synthesis and assembly of synaptic proteins. The importance of MuSK as a synapse organiser is highlighted by cases of autoimmune myasthenia gravis in which MuSK autoantibodies can deplete MuSK from the postsynaptic membrane, leading to complete disassembly of the adult NMJ.

Original languageEnglish
Pages (from-to)295-298
Number of pages4
JournalInternational Journal of Biochemistry and Cell Biology
Volume43
Issue number3
DOIs
Publication statusPublished - Mar 2011
Externally publishedYes

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