Function and regulation of the TRPP3 channel

TRPP3通道的功能和调节

• 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: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629594
• 关键词: Function; regulation; TRPP3; channel

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 Qian and my PhD student Carlos found (unpublished data) that TRPP3 interacts with acid sensing ion channels (ASICs) and glutamate receptors, suggesting its involvement in important cellular functions such as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（TRPP 3）是感觉离子通道TRP超家族的成员。1999年我们首次报道TRPP 3是一种被钙激活的阳离子通道。自2006年以来，有越来越多的证据表明TRPP 3是舌，脑和视网膜中的候选酸传感器，但其确切的生理作用至今仍不清楚。我的博士生JungWoo，Qian和硕士生Wang在一篇论文中发现，TRPP 3与一种名为RACK 1的支架蛋白相互作用，并在功能上受到抑制。Qian和我的博士生卡洛斯发现（未发表的数据）TRPP 3与酸敏感离子通道（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。该计划旨在研究钙和酸诱导的TRPP 3通道激活的机制，TRPP 3与ASIC的相互作用，以及TRPP 3在学习和记忆中的意义，通过这些机制，HQP（如研究生和本科生）将得到培训。假设：1）TRPP 3通过其N-末端的钙依赖性磷酸化被激活，2）TRPP 3和ASIC在表面膜上形成酸敏感通道复合物，和3）TRPP 3或TRPP 3-ASIC复合物对于脑学习和记忆是重要的。项目#1，钙和酸激活TRPP 3的潜在机制。项目#2，TRPP 3与ASIC的物理和功能相互作用。项目#3，TRPP 3或TRPP 3-ASIC相互作用在学习和记忆中的功能意义。我的研究生和本科生将使用细胞和动物模型结合跨学科方法为项目进行实验。意义通过这个项目，我们将获得新的见解钙和酸诱导的TRPP 3通道激活的分子机制，以及通道复合物TRPP 3-ASIC如何参与pH依赖性学习和记忆。该项目与陈博士的其他资助项目一起，将为培养HQP提供优秀的研究课题和环境。