Role of Ca2+ signaling in cell function and diseases

来源:mg真人在线 发布时间 :2019-06-10  阅读次数 :6895

主讲人:Katsuhiko Mikoshiba

主讲人简介(详见附件简历):Katsuhiko Mikoshiba   SIAIS  (Shanghai Institute for Advanced Immunochemical Studies), Shanghai Tech University






Ca2+ plays an essential role in cell function.  It conveys signals to the most important cell process but the detailed mechanism of signaling process is not clearly understood.  We have discovered a key molecule, the IP3  receptor (IP3R) as a P400 protein greatly decreased in the cerebellum of Purkinje cell-degeneration mutant mice, and have subsequently cloned its cDNA. We identified it is endoplasmic reticulum (ER) channel that convert GPCR-IP3 signals to Ca2+ signal at the ER to produce Ca2+ oscillation. We found that IP3R is essential for fertilization, dorso-ventral axis formation, neurite extension, cardiogenesis, exocrine secretion and behavior. We found IP3R interacts ER chaperons to protect from apoptosis caused by ER stress response.  A newly discovered pseudo-IP3 which we named a IRBIT that binds to IP3R and is involved in apoptosis regulation in association with anti-apoptotic proteins. We recently crystalized a large cytosolic domain (2217aa) of IP3R in the presence and absence of IP3  and solved the gating mechanism by biochemical and X-ray crystallographic analysis. We have identified a  “leaflet” structure essential for allosteric channel gating, surrounded by functional molecules that may regulate IP3R activity to balance health and disease.



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