Role of STIM1 in Somatosensation

STIM1 在体感中的作用

基本信息

批准号：
8425974
负责人：
Ardem Patapoutian
金额：
$ 28.43万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-12-03 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8425974
关键词：
Accounting Acute Address Affect Afferent Neurons Analgesics Behavior Biological Assay Biology Calcium Calcium Channel Cell membrane Cells Chemicals Complex Coupled Data Endoplasmic Reticulum Esthesia Family Fever Future Gene Expression Goals Heating Homeostasis Hyperalgesia Hyperthermia Hypothalamic structure Immune Immune system Inflammation Inflammatory Inflammatory Response Ion Channel Knockout Mice Lead Link Mammals Mediating Metabolism Molecular Mus Nature Neurons Nociception Pain Peripheral Phase Play Preoptic Areas Process Proteins Publishing Regulation Role STIM1 gene Signal Pathway Skin System T-Lymphocyte TRPV1 gene Temperature Temperature Sense Thermogenesis Tissues Variant Vasodilation Work capsaicin receptor cell type environmental change experience in vivo keratinocyte natural hypothermia novel preference public health relevance receptor research study response sensor somatosensory

项目摘要

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 However, recent unpublished data from our lab suggests that thermoTRPs are unlikely to explain all of the thermosensory capability of the somatosensory system.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.

描述（由申请人提供）：环境温度变化可能非常剧烈。许多物种，包括哺乳动物，都是恒温的，并严格调节内部温度以实现有效的新陈代谢和生存。为了调节温度稳态，我们进化出了各种感知温度的机制。其中最具有特征的可能是体感神经元的热敏感性——专门用于感知皮肤等周围组织所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，它被证明可以被不同的温度激活，在体感神经元中表达，并且是外周热感觉所必需的。有趣的是，这些thermoTRP 中至少有两种也在角质形成细胞中表达，这表明皮肤细胞参与热感觉。许多thermoTRP 基因敲除小鼠存在热感觉缺陷。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能力。皮肤细胞除了可能参与热感觉之外，还会经历较大的温度变化，并导致炎症和热诱导的血管舒张。此外，其他组织/细胞的热敏感性的分子机制目前尚不清楚。我们最近证明 STIM1/Orai1 离子通道复合物具有敏锐的热敏感性。该提案将建立在这些初步数据的基础上，并追求这些温度敏感离子通道在传感温度中发挥重要作用的一般假设。