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Function and regulation of the TRPP3 channel

TRPP3通道的功能和调节

基本信息

批准号：
401946-2012
负责人：
Chen, XingZhen
金额：
$ 2.62万
依托单位：
University of Alberta
依托单位国家：
加拿大
项目类别：
Discovery Grants Program - Individual
财政年份：
2018
资助国家：
加拿大
起止时间：
2018-01-01 至 2019-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=647408
关键词：
Function regulation TRPP3 channel

项目摘要

Transient receptor potential polycystin-2L1 (TRPP3) is a member of the TRP superfamily of sensory ion channels. It was first reported in 1999 by us that TRPP3 acts as a cation channel activated by calcium. Since 2006 there has been increasing evidence that TRPP3 be a candidate acid sensor in the tongue, brain and retina, but its precise physiological roles have so far remained unclear. My PhD students JungWoo, Qian and MSc student Wang found in a paper in revision (J Biol Chem) that TRPP3 interacts with, and is functionally inhibited by a scaffolding protein called RACK1. Qian and my PhD student Carlos found (unpublished data) that TRPP3 interacts with acid sensing ion channels (ASICs) and glutamate receptors, suggesting its involvement in important cellular functions such as learning and memory. The OBJECTIVES are to study mechanisms underlying the calcium- and acid-induced TRPP3 channel activation, interaction of TRPP3 with ASICs, and implications of TRPP3 in learning and memory, through which HQP such as graduate and undergraduate students will be trained. HYPOTHESES: 1) that TRPP3 is activated by calcium-dependent phosphorylation of its N-terminus, 2) that TRPP3 and ASIC form an acid-sensitive channel complex on the surface membrane, and 3) that TRPP3 or TRPP3-ASIC complex is important for brain learning and memory.** PROJECT #1, mechanisms underlying activation of TRPP3 by calcium and acid. PROJECT #2, physical and functional interaction of TRPP3 with ASICs. PROJECT #3, functional implications of TRPP3 or the TRPP3-ASIC interaction in learning and memory. My graduate and undergraduate students will perform experiments for the projects, using cellular and animal models combined with interdisciplinary approaches.** SIGNIFICANCE. Through this program we will gain novel insights into molecular mechanisms underlying the calcium- and acid-induced TRPP3 channel activation, and how channel complex TRPP3-ASIC is implicated in pH-dependent learning and memory. This program together with other funded projects of Dr. Chen will provide excellent research topics and environments for training HQP.****

瞬时受体电位多囊蛋白-2L1(TRPP3)是Trp超家族感觉离子通道的一员。TRPP3是我们在1999年首次报道的，它是钙激活的阳离子通道。自2006年以来，越来越多的证据表明，TRPP3是舌头、大脑和视网膜的候选酸传感器，但其确切的生理作用迄今尚不清楚。我的博士生JungWoo、Qian和MSC学生Wang在Revision(J Biol Chem)上的一篇论文中发现，TRPP3与TRPP3相互作用，并被一种名为RACK1的支架蛋白功能抑制。钱和我的博士生卡洛斯发现(未发表的数据)，TRPP3与酸感应离子通道(ASIC)和谷氨酸受体相互作用，表明它参与了重要的细胞功能，如学习和记忆。其目的是研究钙和酸诱导的TRPP3通道激活的潜在机制，TRPP3与ASIC的相互作用，以及TRPP3在学习和记忆中的意义，通过这些机制，将培养像研究生和本科生这样的HQP。假设：1)TRPP3是由其N端钙依赖的磷酸化激活的，2)TRPP3和ASIC在表面膜上形成一个酸敏感的通道复合体，3)TRPP3或TRPP3-ASIC复合体对大脑学习和记忆是重要的。**项目1，钙和酸激活TRPP3的机制。项目2，TRPP3与ASIC的物理和功能相互作用。项目3，TRPP3或TRPP3-ASIC相互作用在学习和记忆中的功能含义。我的研究生和本科生将使用细胞和动物模型结合跨学科的方法，为这些项目进行实验。**意义。通过这个项目，我们将获得新的见解，以了解钙和酸诱导的TRPP3通道激活的分子机制，以及通道复合体TRPP3-ASIC如何参与pH依赖的学习和记忆。该计划与陈博士的其他资助项目将为培训HQP提供优秀的研究课题和环境。*