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

报告时间：6月11日（周二）13:30-14:30

报告地点：闵行校区生命科学技术学院1号楼105会议室

联系人：李胜天副教授

报告简介：

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.

代表性论文：

Nature 342(6245):32-8. (1989)　　Science 257:251-5. (1992)　Cell  73  555-570  (1993)　Nature 379(6561):168-71. (1996)　Science 278(5345):1940-3. (1997)　Science 282:1705-1708. (1998)　Nat. Biotechnol. 20 87-90 (2002)　Nature 417:295-299. (2002)　Cell 120(1):85-98. (2005)　Science 309(5744):2232-4. (2005)　Molecular Cell 22(6):795-806. (2006)　Neuron 68(5):865-78. (2010)　Nature Methods 7:729-732. (2010)　eLife DOI10.7554/eLife19896 (2016)　Nature Comm (2016) doi: 10.1038/ncomms11100.

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