Musk
Developmental stage
Skeletal myogenesis is a major site of expression during normal embryogenesis. In addition, the ganglia of the developing peripheral nervous system and various embryonic epithelia, including those of kidney, lung and gut are also sites of expression.
Function
Receptor tyrosine kinase which plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and the skeletal muscle. Recruitment of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation and activation of MUSK, the kinase of the complex. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. May regulate AChR phosphorylation and clustering through activation of ABL1 and Src family kinases which in turn regulate MUSK. DVL1 and PAK1 that form a ternary complex with MUSK are also important for MUSK-dependent regulation of AChR clustering. May positively regulate Rho family GTPases through FNTA. Mediates the phosphorylation of FNTA which promotes prenylation, recruitment to membranes and activation of RAC1 a regulator of the actin cytoskeleton and of gene expression. Other effectors of the MUSK signaling include DNAJA3 which functions downstream of MUSK. May also play a role within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation.
Post-translational modifications
Ubiquitinated by PDZRN3. Ubiquitination promotes endocytosis and lysosomal degradation.
Phosphorylated (PubMed:16818610). Phosphorylation is induced by AGRIN (PubMed:18848351, PubMed:8653787). Autophosphorylated. Autophosphorylation at Tyr-553 is required for interaction with DOK7 which in turn stimulates the phosphorylation and the activation of MUSK (PubMed:16794080, PubMed:20603078).
Neddylated.
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family.
Tissue Specificity
Expressed preferentially in skeletal muscle.
Cellular localization
- Postsynaptic cell membrane
- Single-pass type I membrane protein
- Localizes to the postsynaptic cell membrane of the neuromuscular junction.
Alternative names
Nsk2, Musk, Muscle-specific tyrosine-protein kinase receptor, MuSK, Muscle-specific kinase receptor