Muscle specific kinase: organiser of synaptic membrane domains.
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.
Ghazanfari
Nazanin
N
Physiology and Bosch Institute, Anderson Stuart Bldg (F13), The University of Sydney, Sydney, NSW 2006, Australia. nazanin@physiol.usyd.edu.au
Fernandez
Kristine J
KJ
Murata
Yui
Y
Morsch
Marco
M
Ngo
Shyuan T
ST
Reddel
Stephen W
SW
Noakes
Peter G
PG
Phillips
William D
WD
D000818:Animals; D001327:Autoimmune Diseases / Q000201:enzymology; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D009132:Muscles / Q000201:enzymology*; D009928:Organ Specificity; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism*
D020794:Receptor Protein-Tyrosine Kinases