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.
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)
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