title: The Ig1/2 domain of MuSK binds to muscle surface and is involved in acetylcholine receptor clustering.
abstract: The neuromuscular junction, the synapse between motor neurons and muscle cells, serves as an excellent model for studying synapse formation. Agrin is believed to be released by motor neurons to induce postsynaptic differentiation at the neuromuscular junction. MuSK, a receptor tyrosine kinase, appears to be a key component of the agrin receptor complex. However, how agrin activates MuSK remains unclear. To address this question, we characterized the binding of the MuSK extracellular region to the muscle cell surface. The MuSK ectodomain was found to bind to muscle cells in a manner dependent on stimulation with neural agrin. Moreover, the binding was myotube specific and appeared to be mediated by two regions in the MuSK: one region containing the first and second immunoglobin domains and the other containing the cysteine-rich domain. Importantly, recombinant proteins containing the binding activity can block full-length MuSK binding to muscle cells and agrin-induced AChR clustering. These results suggest that the Ig1/2 domain of MuSK is involved in AChR clustering by binding to the muscle surface.
authors.affiliation: Program of Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Ye Elaine
authors.initials: YE
authors.lastname: Wang
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Xiong
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000502:physiology; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D011940:Receptor Aggregation; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011950:Receptors, Cholinergic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D007074:Immunoglobulin G; D011950:Receptors, Cholinergic; C511695:MuSK protein, mouse; D020794:Receptor Protein-Tyrosine Kinases