Takeshima H, Shimuta M, Komazaki S, Ohmi K, Nishi M, Iino M, Miyata A, Kangawa K
Department of Pharmacology, Faculty of Medicine, University of Tokyo, and CREST, Japan Science and Technology Corporation, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.
Biochem J. 1998 Apr 1;331 ( Pt 1)(Pt 1):317-22. doi: 10.1042/bj3310317.
In skeletal muscle, excitation-contraction (E-C) coupling requires the conversion of the depolarization signal of the invaginated surface membrane, namely the transverse (T-) tubule, to Ca2+ release from the sarcoplasmic reticulum (SR). Signal transduction occurs at the junctional complex between the T-tubule and SR, designated as the triad junction, which contains two components essential for E-C coupling, namely the dihydropyridine receptor as the T-tubular voltage sensor and the ryanodine receptor as the SR Ca2+-release channel. However, functional expression of the two receptors seemed to constitute neither the signal-transduction system nor the junction between the surface and intracellular membranes in cultured cells, suggesting that some as-yet-unidentified molecules participate in both the machinery. In addition, the molecular basis of the formation of the triad junction is totally unknown. It is therefore important to examine the components localized to the triad junction. Here we report the identification using monoclonal antibody and primary structure by cDNA cloning of mitsugumin29, a novel transmembrane protein from the triad junction in skeletal muscle. This protein is homologous in amino acid sequence and shares characteristic structural features with the members of the synaptophysin family. The subcellular distribution and protein structure suggest that mitsugumin29 is involved in communication between the T-tubular and junctional SR membranes.
在骨骼肌中，兴奋 - 收缩（E - C）偶联需要将内陷表面膜（即横管，T管）的去极化信号转化为肌浆网（SR）释放Ca2+。信号转导发生在T管和SR之间的连接复合体处，即三联体连接，其中包含E - C偶联所必需的两个成分，即作为T管电压传感器的二氢吡啶受体和作为SR Ca2+释放通道的兰尼碱受体。然而，在培养细胞中，这两种受体的功能性表达似乎既不构成信号转导系统，也不构成表面膜与内膜之间的连接，这表明一些尚未鉴定的分子参与了这两种机制。此外，三联体连接形成的分子基础完全未知。因此，研究定位于三联体连接的成分很重要。在此，我们报告了使用单克隆抗体的鉴定以及通过cDNA克隆对mitsugumin29的一级结构的研究，mitsugumin29是一种来自骨骼肌三联体连接的新型跨膜蛋白。该蛋白在氨基酸序列上具有同源性，并且与突触小泡蛋白家族成员具有共同的结构特征。亚细胞分布和蛋白质结构表明mitsugumin29参与了T管和连接性SR膜之间的通讯。
