Molecular Characterization of ANKTM1

描述（由申请人提供）：本提案的总体目标是帮助我们理解我们如何感知我们的环境。具体地说，我将研究那些促进我们对温度和锅的感知的系统。最近，许多trp家族的非特异性阳离子通道（TRPc）成员被证明在不同的温度范围内被激活。TRPV1是第一个被发现的热敏TRPc，被有害的热激活，并在炎症诱导的热痛觉过敏中发挥作用。trpc被温度激活的分子机制目前尚不清楚。ANKTM1是一种假定的多模伤害感受器，最近被鉴定为一种TRP通道，当与brandykinin受体共表达时，它对有害水平的寒冷、有害化合物肉桂醛、炎症肽brandykinin作出反应，并在伤害感觉神经元的一个亚群中表达。本提案的目标是确定ANKTM1中赋予感知有毒寒冷和/或肉桂醛能力的特定残基/结构域。这些研究结果将提供对ANKTM1激活机制的基本理解，并可能为温度如何抑制TRP通道激活提供一般见解。这项研究也可能有助于基于识别伤害感受器ANKTM1的潜在靶点来开发治疗疼痛的药物

DESCRIPTION (provided by applicant): The broad objective of this proposal is to contribute to our understanding of how we perceive our environment. Specifically, I will be examining the systems that facilitate our perception of temperature and pan. Recently, numerous members of the TRP-family of non-specific cation channels (TRPc) have been shown to be activated in response to different ranges of temperature. TRPV1, the first thermo sensitive TRPc identified, is activated by noxious heat and has a demonstrated role in inflammation induced thermal hyperalgesia. The molecular mechanisms by which TRPcs are activated by temperature are currently unknown. ANKTM1, a putative polymodal nociceptor was recently identified as a TRP channel that responds to noxious levels of cold, the noxious compound cinnamaldehyde, the inflammatory peptide brandykinin when co-expressed with the brandykinin receptor and is expressed in a subset of nociceptive sensory neurons. The goals of this proposal are to identify specific residues/domains within ANKTM1 that confer the ability to sense noxious cold and/or cinnamaldehyde. The findings from these studies will provide a basic understanding of the mechanisms of ANKTM1 activation and may provide general insight into how temperature gates TRP channel activation. This research may also contribute to the development of therapeutic drugs to manage pain based on the identification of potential targets on the nociceptor, ANKTM1