Molecular Characterization of ANKTM1

描述(由申请者提供)：这项建议的广泛目标是帮助我们理解我们如何感知我们的环境。具体地说，我将研究有助于我们感知温度和PAN的系统。最近，非特异性阳离子通道(TrPc)家族中的许多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性TRPc，它被有毒的高温激活，并在炎症诱导的热痛敏中发挥作用。温度激活TRPcs的分子机制目前尚不清楚。ANKTM1是一种可能的多模式伤害性感受器，最近被发现是一种Trp通道，当与Brandykinin受体共表达时，它可以对伤害水平的寒冷、有毒化合物肉桂醛、炎症性多肽Brandykinin做出反应，并在一系列伤害性感觉神经元中表达。这项建议的目标是确定ANKTM1中具有感知有害寒冷和/或肉桂醛能力的特定残基/结构域。这些研究的结果将提供对ANKTM1激活机制的基本了解，并可能为温度门如何激活Trp通道提供一般的洞察。这项研究还可能有助于基于伤害性感受器ANKTM1上潜在靶点的疼痛治疗药物的开发

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