Molecular Characterization of ANKTM1

描述（由申请人提供）：本提案的广泛目标是帮助我们了解我们如何看待我们的环境。具体来说，我将研究促进我们对温度和锅的感知的系统。最近，非特异性阳离子通道（TRPc）的TRP家族的许多成员已被证明在不同的温度范围内被激活。TRPV 1是第一个被发现的热敏性TRPc，被有害热激活，并在炎症诱导的热痛觉过敏中发挥作用。TRPcs被温度激活的分子机制目前尚不清楚。ANKTM 1是一种假定的多模态伤害感受器，最近被鉴定为TRP通道，当与布兰迪激肽受体共表达时，其响应于有害水平的冷、有害化合物肉桂醛、炎性肽布兰迪激肽，并且在伤害感受感觉神经元的子集中表达。该提议的目标是鉴定ANKTM 1内赋予感测有害冷和/或肉桂醛的能力的特定残基/结构域。这些研究的结果将提供对ANKTM 1激活机制的基本理解，并可能提供对温度门控TRP通道激活的一般见解。这项研究也可能有助于开发基于伤害感受器ANKTM 1上潜在靶点的治疗药物来管理疼痛。

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