title: Structure and activation of MuSK, a receptor tyrosine kinase central to neuromuscular junction formation.
abstract: MuSK (muscle-specific kinase) is a receptor tyrosine kinase that plays a central signaling role in the formation of neuromuscular junctions (NMJs). MuSK is activated in a complex spatio-temporal manner to cluster acetylcholine receptors on the postsynaptic (muscle) side of the synapse and to induce differentiation of the nerve terminal on the presynaptic side. The ligand for MuSK is LRP4 (low-density lipoprotein receptor-related protein-4), a transmembrane protein in muscle, whose binding affinity for MuSK is potentiated by agrin, a neuronally derived heparan-sulfate proteoglycan. In addition, Dok7, a cytoplasmic adaptor protein, is also required for MuSK activation in vivo. This review focuses on the physical interplay between these proteins and MuSK for activation and downstream signaling, which culminates in NMJ formation. This article is part of a Special Issue entitled: Emerging recognition and activation mechanisms of receptor tyrosine kinases.
authors: Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA. Electronic address: stevan.hubbard@med.nyu.edu.
authors: Stevan R
authors: SR
authors: Hubbard
authors: Kavitha
authors: K
authors: Gnanasambandan
mesh_terms: D018171:Agrin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009411:Nerve Endings / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: D018171:Agrin; C511692:DOK7 protein, human; D026502:LDL-Receptor Related Proteins; C551781:LRP4 protein, human; D009124:Muscle Proteins; D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases
keywords: Acetylcholine receptor; Agrin; LRP4; MuSK; Neuromuscular junction