Molecular contraction of Ca^<2+> signaling

在可兴奋细胞中，细胞表面膜的去极化信号通过细胞内Ca^2+库转化为细胞质Ca^2+信号。我研究的最终目标是了解信号转换机制的分子结构，在这个项目中，我主要关注兰尼碱受体作为细胞内Ca^2+释放通道的功能和细胞内Ca^2+储存的分子组成。在关于兰尼碱受体的实验中，通道失活的Ca^2+结合位点被定位在一级结构上，并且在骨骼肌细胞中三联体连接中兰尼碱受体亚型的共存已经被确定。另一方面，目前已经鉴定出新的膜蛋白，即mitsugumins。Mitsugumin 29是一个具有4个跨膜片段的syanptophisin家族的新成员。当骨骼肌细胞缺乏mitsugumin 29时，三联体连接不能正确构建，因此兴奋-收缩偶联的效率降低。嗜连接蛋白（mitsugumin 72）由识别细胞表面膜的胞浆区和跨越Ca^2+储存膜的跨膜段组成。当心肌缺乏亲连接蛋白时，细胞表面膜和Ca^2+库之间的连接膜结构发育不良，由此产生的异常Ca^2+信号传导导致胚胎期心力衰竭。

In excitable cells, the depolarization signal of cell-surface membrane is converted into cytoplasmic Ca^<2+> signaling using intracellular Ca^<2+> stores. The final goal of my study is to understand the molecular architecture of the signal conversion machinery, and in this project I focused on the function of the ryanodine receptor as an inracellular Ca^<2+> release channel and the molecular components of intracellular Ca^<2+> stores. In experiments on the ryanodine receptor, a Ca^<2+>-binding site for channel inactivation has been mapped on the primary structure, and co-existence of ryanodine receptor subtypes in the triad junction has been defined in skeletal muscle cells. On the other hands, novel membrane proteins namely mitsugumins have been identified currently. Mitsugumin29 is a novel member of the syanptophisin family bearing 4 transmembrane segments. When skeletal muscle cells lacked mitsugumin29, triad junctions could not be constructed correctly and thus efficiency of excitation-contraction coupling reduced. Junctophilin (mitsugumin72) is composed of the cytoplasmic region recognizing the cell-surface membrane and the transmembrane segment spanning the Ca^<2+> store membrane. When cardiac muscle lacked junctophilin, junctional membrane structures between the cell-surface membrane and Ca^<2+> store were poorly developed and resulting abnormal Ca^<2+> signaling resulted in heart failure during embryonic stages.