Muscle Specific Kinase: Organiser of synaptic membrane domains

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• 作者：Nazanin Ghazanfari^a ; ^{nazanin@physiol.usyd.edu.au} ; Kristine J. Fernandez^a ; ^{kfer7988@physiol.usyd.edu.au} ; Yui Murata^a ; ^{ymur7519@uni.sydney.edu.au} ; Marco Morsch^a ; ^{mm@physiol.usyd.edu.au} ; Shyuan T. Ngo^b ; ^{s.ngo@uq.edu.au} ; Stephen W. Reddel^c ; ^{stephenr@med.usyd.edu.au} ; Peter G. Noakes^b ; ^{p.noakes@uq.edu.au} ; William D. Phillips^a ; ^{william.phillips@sydney.edu.au}
• 关键词：MuSK ; LRP4 ; Synapse formation ; Tyrosine kinases ; Agrin
• 刊名：The International Journal of Biochemistry and Cell Biology
• 出版年：2011
• 出版时间：March 2011
• 年：2011
• 卷：43
• 期：3
• 页码：295-298
• 全文大小：508 K

文摘

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.