"TRPC4 integrates multiple transmitter signals to regulate neuronal function"朱曦 博士(The University of Texas Health Science Center at Houston)-2016.5.27

"TRPC4 integrates multiple transmitter signals to regulate neuronal function"朱曦 博士(The University of Texas Health Science Center at Houston)-2016.5.27

时间:  2016年5月27日  14:00
地点:中北校区 脑功能基因组学研究所一楼会议室
报告题目:TRPC4 integrates multiple transmitter signals to regulate neuronal function
报告人:朱曦 博士(The University of Texas Health Science Center at Houston)
主持人:殷东敏 教授


报告人简介:Michael Xi Zhu is professor of Department of Integrative Biology and Pharmacology, the University of Texas Health Science Center at Houston, Houston, Texas. He received his Ph.D. in Biochemistry in 1991 from University of Houston and did his postdoctoral training in Cellular and Molecular Biology from 1991-1994 at Baylor College of Medicine. He then worked as an Assistant Researcher in the Department of Anesthesiology, UCLA, from 1994 to 1997. In Autumn of 1997, he went to the Ohio State University to build his own lab and moved from the rank of Assistant Professor to Full Professor in the Department of Neuroscience there. In 2010, he moved to his current position at the University of Texas-Houston.  Dr. Zhu’s research interests include several aspects of cell signaling, especially those that involve heterotrimeric G proteins and ion channels that affect Ca2+ signaling.  He has published more than 120 research papers, reviews, and monographs on these topics and delivered lectures at many international conferences and symposia.  Dr. Zhu’s main contributions include identification and characterization of multiple TRPC channels in mammalian species and determination of the molecular identity of endolysosomal Ca2+ release channels activated by the Ca2+ mobilizing messenger, NAADP.  Dr. Zhu is a regular member of the Biophysical Society, Aspet and ASMBM. He is an Associate Editor of Journal of Cellular Physiology and a member of editorial boards of Pflügers Archiv, Biophysics Reports and Molecular Pharmacology. He served as a regular member of the US NIH Molecular and Integrative Signal Transduction study section from 2010-2014. Dr. Zhu has been involved in setting up the International Scientist Workstation of Neuropharmacology at Shanghai Institute of Materia Medica, Chinese Academy of Sciences. He has served as a Distinguished Investigator there since 2011.


报告简介:Transient Receptor Potential Canonical (TRPC) proteins form non-selective cation channels commonly known to be activated downstream from receptors that signal through phospholipase C (PLC). Although TRPC3/C6/C7 can be directly activated by diacylglycerols produced by PLC hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), the mechanism by which the PLC pathway activates TRPC4/C5 remains unclear. We show that coincident stimulation of Gi/o proteins and PLCδ1 is necessary and sufficient for activation of TRPC4 expressed in HEK293 cells. In addition, while the TRPC4 currents were dependent on intracellular Ca2+ and PIP2, both Ca2+ and PIP2 also exhibited inhibitory effects on the channel. TRPC4 channel activation was strongly suppressed by a dominant-negative PLCδ1 mutant or a constitutively active RhoA mutant. In native neurons, TRPC4-containing channels are co-regulated by Gi/o proteins and receptors that signal through PLC, and Ca2+. The coincident detection of inputs from multiple neurotransmitters and neurotrophins defines the neurological functions of TRPC4-containing channels in neural development, synaptic transmission and neurodegeneration. We propose that TRPC4 modulates brain functions by integrating signals from multiple neurotransmitter inputs from different pathways in normal and pathophysiological conditions.