title: Mesdc2 plays a key role in cell-surface expression of Lrp4 and postsynaptic specialization in myotubes.
abstract: Low-density lipoprotein receptor-related protein 4 (Lrp4) is essential for pre- and post-synaptic specialization at the neuromuscular junction (NMJ), an indispensable synapse between a motor nerve and skeletal muscle. Muscle-specific receptor tyrosine kinase MuSK must form a complex with Lrp4 to organize postsynaptic specialization at NMJs. Here, we show that the chaperon Mesdc2 binds to the intracellular form of Lrp4 and promotes its glycosylation and cell-surface expression. Furthermore, knockdown of Mesdc2 suppresses cell-surface expression of Lrp4, activation of MuSK, and postsynaptic specialization in muscle cells. These results suggest that Mesdc2 plays an essential role in NMJ formation by promoting Lrp4 maturation.
authors.affiliation: Division of Genetics, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Hoshi
authors.forename: Tohru
authors.initials: T
authors.lastname: Tezuka
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Shun-ichiro
authors.initials: S
authors.lastname: Iemura
authors.forename: Tohru
authors.initials: T
authors.lastname: Natsume
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamanashi
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D026502:LDL-Receptor Related Proteins; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D034741:RNA, Small Interfering; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*
chemical_list: D026502:LDL-Receptor Related Proteins; C116415:Lrp4 protein, mouse; C472170:MESD protein, mouse; D018832:Molecular Chaperones; D034741:RNA, Small Interfering; D011973:Receptors, LDL; C511695:MuSK protein, mouse; D020794:Receptor Protein-Tyrosine Kinases
keywords: ACh; ACh receptor; AChR; Btx; CMS; Chaperon; DPAGT1; Dok-7; GFPT1; Glycosylation; LC–MS/MS; Lrp4; Mesdc2; MuSK; NMJ; Neuromuscular junction; TM; WCL; acetylcholine; bungarotoxin; congenital myasthenic syndrome; dolichyl-phosphate (UDP-N-acetylglucosamine) N-acetylglucosaminephosphotransferase 1; downstream of tyrosine kinases 7; glutamine–fructose-6-phosphate transaminase 1; liquid chromatography–tandem mass spectrometry; low-density lipoprotein receptor-related protein 4; mesoderm development candidate 2; muscle-specific kinase; neuromuscular junction; tunicamycin; whole cell lysates