Mu SK Protein - MuSK Is Required For Formation of The Neuromuscular Junction

MuSK Is Required For Formation of The Neuromuscular Junction

During development, the growing end of motor neuron axons secrete a protein called agrin. This protein binds to several receptors on the surface of skeletal muscle. The receptor that seems to be required for formation of the neuromuscular junction (NMJ), which comprises the nerve-muscle synapse, is called MuSK (Muscle-specific kinase). MuSK is a receptor tyrosine kinase - meaning that it induces cellular signaling by causing the addition of phosphate molecules to particular tyrosines on itself, and on proteins that bind the cytoplasmic domain of the receptor.

The requirement for MuSK in the formation of the NMJ was demonstrated primarily by mouse ("knockout") studies. In mice that are deficient for either agrin or MuSK, the neuromuscular junction does not form. Many other proteins also comprise the NMJ, and are required to maintain its integrity. For example, MuSK also binds a protein called "downstream-of-tyrosine-kinase-7" (Dok-7). Dok-7's PTB domain binds phosphorylated MuSK, which acts to stabilize active MuSK or alternatively enhance MuSK's own kinase activity.

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