Function and regulation of the TRPP3 channel

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的N端钙依赖性磷酸化激活；2)TRPP3和ASIC在膜表面形成酸敏通道复合体；3)TRPP3或TRPP3-ASIC复合体对大脑学习和记忆起重要作用。

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 Qian and my PhD student Carlos found (unpublished data) that TRPP3 interacts with acid sensing ion channels (ASICs) and glutamate receptors, suggesting its involvement in important cellular functions such as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.