MuSK (for Muscle-Specific Kinase) is a
receptor tyrosine kinase
Receptor tyrosine kinases (RTKs) are the high- affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kin ...
required for the formation and maintenance of the
neuromuscular junction. It is activated by a nerve-derived
proteoglycan called
agrin
Agrin is a large proteoglycan whose best-characterised role is in the development of the neuromuscular junction during embryogenesis. Agrin is named based on its involvement in the aggregation of acetylcholine receptors during synaptogenesis. ...
, which is similarly also required for neuromuscular junction formation.
MuSK signaling
Upon activation by its ligand
agrin
Agrin is a large proteoglycan whose best-characterised role is in the development of the neuromuscular junction during embryogenesis. Agrin is named based on its involvement in the aggregation of acetylcholine receptors during synaptogenesis. ...
, MuSK signals via the proteins called
casein kinase 2
Casein kinase 2 ()(CK2/CSNK2) is a serine/threonine-selective protein kinase that has been implicated in cell cycle control, DNA repair, regulation of the circadian rhythm, and other cellular processes. De-regulation of CK2 has been linked to tumo ...
(CK2),
Dok-7 Dok-7 is a non-catalytic cytoplasmic adaptor protein that is expressed specifically in muscle and is essential for the formation of neuromuscular synapses. Further, Dok-7 contains pleckstrin homology (PH) and phosphotyrosine-binding (PTB) domains ...
and
rapsyn
43 kDa receptor-associated protein of the synapse (rapsyn) is a protein that in humans is encoded by the ''RAPSN'' gene.
Function
This protein belongs to a family of proteins that are receptor associated proteins of the synapse. It contains a ...
, to induce "clustering" of acetylcholine receptors (
AChR
An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.
Classification
Like other transmembrane receptors, acetylcholine receptors are classified accordin ...
). Both CK2 and Dok-7 are required for MuSK-induced formation of the
neuromuscular junction, since mice lacking Dok-7 failed to form AChR clusters or neuromuscular synapses, and since downregulation of CK2 also impedes recruitment of AChR to the primary MuSK scaffold. In addition to the proteins mentioned, other proteins are then gathered, to form the endplate to the neuromuscular junction. The nerve terminates onto the endplate, forming the neuromuscular junction - a structure required to transmit nerve impulses to the muscle, and thus initiating muscle contraction.
Role in disease
Antibodies directed against this protein (Anti-MuSK autoantibodies) are found in some people with
myasthenia gravis not demonstrating antibodies to the
acetylcholine receptor
An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.
Classification
Like other transmembrane receptors, acetylcholine receptors are classified according ...
. The disease still causes loss of acetylcholine receptor activity,
but the symptoms affected people experience may differ from those of people with other causes of myasthenia gravis.
References
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Tyrosine kinase receptors
Developmental neuroscience
Proteins