3hkl

Structural highlights

Function

MUSK_RAT 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.^{[1] [2]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Tyrosine kinase receptor 3D structures

References

1. ↑ Garcia-Osta A, Tsokas P, Pollonini G, Landau EM, Blitzer R, Alberini CM. MuSK expressed in the brain mediates cholinergic responses, synaptic plasticity, and memory formation. J Neurosci. 2006 Jul 26;26(30):7919-32. PMID:16870737 doi:http://dx.doi.org/10.1523/JNEUROSCI.1674-06.2006
2. ↑ Stiegler AL, Burden SJ, Hubbard SR. Crystal structure of the agrin-responsive immunoglobulin-like domains 1 and 2 of the receptor tyrosine kinase MuSK. J Mol Biol. 2006 Dec 1;364(3):424-33. Epub 2006 Sep 12. PMID:17011580 doi:10.1016/j.jmb.2006.09.019
3. ↑ Stiegler AL, Burden SJ, Hubbard SR. Crystal structure of the frizzled-like cysteine-rich domain of the receptor tyrosine kinase MuSK. J Mol Biol. 2009 Oct 16;393(1):1-9. Epub 2009 Aug 4. PMID:19664639 doi:10.1016/j.jmb.2009.07.091