Role of STIM1 in Somatosensation

描述（由申请人提供）：环境温度变化可能极端。许多物种，包括哺乳动物，都是恒温动物，为了有效的新陈代谢和生存，它们严格调节内部温度。为了调节温度稳态，我们进化出了各种感知温度的机制。也许其中最具特征的是体感神经元的热敏性-专门感知周围组织（如皮肤）反映的环境温度变化。瞬时受体电位（TRP）离子通道家族的一个子集被称为thermoTRP，被证明是由不同的温度激活，在体感神经元中表达，并且是外周温度感觉所需的。有趣的是，这些thermoTRP中至少有两种也在角质形成细胞中表达，暗示皮肤细胞具有温度感觉。许多thermoTRP敲除小鼠具有热敏缺陷。然而，我们实验室最近未发表的数据表明，thermoTRP不太可能解释体感系统的所有热感觉能力。皮肤细胞经历广泛的温度变化，并有助于炎症和热诱导的血管舒张，除了潜在地参与温度感觉。此外，其他组织/细胞的热敏性的分子机制目前尚不清楚。我们最近发现，STIM 1/Orai 1离子通道复合物是急性热敏性的。这项建议将建立在这些初步数据和追求的一般假设，这些温度敏感的离子通道在传感温度发挥重要作用。

DESCRIPTION (provided by applicant): Environmental temperature variations can be extreme. Many species, including mammals, are homeothermic, and tightly regulate internal temperatures for efficient metabolism and survival. To regulate temperature homeostasis, we have evolved various mechanisms to sense temperature. Perhaps best characterized among these is the thermosensitivity of somatosensory neurons - specialized to sense environmental changes in temperature as reflected in peripheral tissues such as the skin. A subset of Transient Receptor Potential (TRP) family of ion channels dubbed thermoTRPs are shown to be activated by distinct temperatures, are expressed in somatosensory neurons, and are required for peripheral thermosensation. Interestingly, at least two of these thermoTRPs are also expressed in keratinocytes, implicating skin cells in thermosensation. Many of the thermoTRP knockout mice have thermosensory deficits. However, recent unpublished data from our lab suggests that thermoTRPs are unlikely to explain all of the thermosensory capability of the somatosensory system. Skin cells experience wide temperature variations and contribute to inflammation and heat-induced vasodilation, in addition to potentially being involved in thermosensation. Furthermore, the molecular mechanism of thermosensitivity of other tissues/cells is not currently known. We have recently shown that STIM1/Orai1 ion channel complex is acutely thermosensitive. This proposal will build on these preliminary data and pursue the general hypothesis that these temperature- sensitive ion channels play an essential role in sensing temperature.