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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Proc Natl Acad Sci U S A. 114(18): 4661-4666. (2017)
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