Mesdc2 plays a key role in cell-surface expression of Lrp4 and postsynaptic specialization in myotubes.

Mesdc2 在 Lrp4 的细胞表面表达和肌管突触后特化中起关键作用。

• 影响指数: 3.864
• 发表时间: Nov 2013 29
• 来源期刊: FEBS Lett
• DOI: 10.1016/j.febslet.2013.10.001
• PMID: 24140340
• 文章类型: Journal Article
• 中科院分区: Q3
• 方向: 生物
• 作者列表: Hoshi T,Tezuka T,Yokoyama K,Iemura S,Natsume T,Yamanashi Y

关键词: 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

Mesh: Animals; Cell Differentiation; Cell Membrane / metabolism; Glycosylation; HEK293 Cells; Humans; LDL-Receptor Related Proteins; Mice; Molecular Chaperones / genetics metabolism; Muscle Fibers, Skeletal / cytology metabolism; Myoblasts / cytology metabolism; Neuromuscular Junction / metabolism; Protein Processing, Post-Translational; Protein Transport; RNA, Small Interfering; Receptor Protein-Tyrosine Kinases / metabolism; Receptors, LDL / genetics metabolism

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.

摘要

低密度脂蛋白受体相关蛋白4（Lrp4）对于神经肌肉接头（NMJ）的突触前和突触后特化至关重要，运动神经和骨骼肌之间不可缺少的突触。肌肉特异性受体酪氨酸激酶MuSK必须与Lrp4形成复合物，以组织NMJ的突触后特化。这里,我们表明，分子伴侣Mesdc2与Lrp4的细胞内形式结合，并促进其糖基化和细胞表面表达。此外，Mesdc2的敲低抑制Lrp4的细胞表面表达，MuSK的激活，和肌肉细胞的突触后特化。这些结果表明Mesdc2通过促进Lrp4成熟在NMJ形成中起重要作用。