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小鼠肌肉中乙酰胆碱受体γ亚基的两种形式。

Two forms of acetylcholine receptor gamma subunit in mouse muscle.

作者信息

Mileo A M, Monaco L, Palma E, Grassi F, Miledi R, Eusebi F

机构信息

Laboratorio di Biofisica, Centro Ricerca Sperimentale, IRE, Rome, Italy.

出版信息

Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2686-90. doi: 10.1073/pnas.92.7.2686.

Abstract

Nicotinic acetylcholine receptors (nAcChoRs) of skeletal muscle are heterosubunit ligand-gated channels that mediate signal transmission from motor nerves to muscle. While cloning murine nAcChoR subunits, to gain an insight into the receptor diversity across species, we detected two forms of gamma subunits in the myogenic C2C12 cell line. Both forms are functional when expressed in Xenopus oocytes. One gamma subunit [long gamma (gamma 1)] was almost identical to that previously cloned in the murine BC3H-1 tumor cell line. The second form of gamma subunit [short gamma (gamma s)] lacked 156 bp (52 amino acids) in the extracellular N terminus, adjoining the hydrophobic segment M1, which corresponds to the fifth exon of the gamma-subunit gene. The two forms of gamma subunit coexist during myogenesis in vitro and in 17-day embryonic and denervated adult muscle fibers in vivo. However, the gamma s variant was the only form of gamma subunit in newborn muscle. In dissociated muscle fibers of newborn mice, AcCho-evoked channel openings were more prolonged when compared with C2C12 myotubes or denervated adult muscle fibers. The gamma s subunit may, thus, contribute to the structural and functional diversity of nAcChoRs in muscle cells.

摘要

骨骼肌的烟碱型乙酰胆碱受体(nAcChoRs)是异源亚基配体门控通道,介导从运动神经到肌肉的信号传递。在克隆小鼠nAcChoR亚基以深入了解物种间受体多样性的过程中,我们在成肌C2C12细胞系中检测到两种形式的γ亚基。两种形式在非洲爪蟾卵母细胞中表达时均具有功能。一种γ亚基[长γ(γ1)]与先前在小鼠BC3H - 1肿瘤细胞系中克隆的几乎相同。第二种γ亚基形式[短γ(γs)]在细胞外N端毗邻疏水片段M1处缺少156 bp(52个氨基酸),这对应于γ亚基基因的第五外显子。两种形式的γ亚基在体外成肌过程中以及体内17天胚胎和去神经支配的成年肌纤维中共存。然而,γs变体是新生肌肉中γ亚基的唯一形式。在新生小鼠的解离肌纤维中,与C2C12肌管或去神经支配的成年肌纤维相比,乙酰胆碱(AcCho)诱发的通道开放持续时间更长。因此,γs亚基可能有助于肌肉细胞中nAcChoRs的结构和功能多样性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9075/42283/3f75b1312f45/pnas01485-0280-a.jpg

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