Molecular characterization of Sensory Function

感觉功能的分子表征

• 批准号: 7024527
• 负责人: Ardem Patapoutian
• 金额: $ 42.39万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7024527
• 关键词: biological signal transduction; capsaicin; cell membrane; chronic pain; cold temperature; electrophysiology; gene expression; genetically modified animals; histopathology; in situ hybridization; laboratory mouse; membrane channels; membrane potentials; neurogenetics; northern blottings; pain threshold; polymerase chain reaction; sensation; sensory mechanism; sensory receptors; spinal ganglion; thermogenesis; thermoreception; tissue /cell culture; touch

DESCRIPTION (provided by applicant): While we usually take sensations such as pain, warmth, or cold for granted, the molecules involved in these processes orchestrate a complex biological response to the outside world and remain almost a complete mystery. The sense of touch consists of the perception of multiple discrete types of thermal, mechanical, and chemical stimuli. A great deal remains unknown about the genes involved in sensing these stimuli. With the completion of the human genome project, we have powerful new methods to identify these elusive sensory molecules. Using such tools, we recently cloned the first gene involved in our ability to sense cold temperatures. Trpm8, encodes for a protein present at the plasma membrane of cold-sensing neurons that belongs to the Transient Receptor Potential (TRP) channel family. More recently, we have identified a novel sensory channel that responds to colder temperatures, ANKTM1. ANTKM1 is distantly related to TRPM8 and is one of six TRP family members to sense temperature. The cold-activated TRP channels allow positive charged ions into the cell as the external temperature reaches a critical threshold. We wish to understand much more about this activation process. Most fundamentally, how do these channels actually sense cold temperature at the molecular level? TRP channels may respond to thermal stimuli using completely novel mechanisms than those involved in classical ligand-gated channels. Finally, we will ask if these channels are required for cold detection and pain sensation in-vivo.

描述（由申请人提供）：虽然我们通常认为疼痛，温暖或寒冷等感觉是理所当然的，但参与这些过程的分子对外界做出了复杂的生物反应，并且几乎仍然是一个完全的谜。触觉包括对多种离散类型的热、机械和化学刺激的感知。关于参与感知这些刺激的基因，还有很多未知数。随着人类基因组计划的完成，我们有了强大的新方法来识别这些难以捉摸的感觉分子。利用这些工具，我们最近克隆了第一个与我们感知寒冷温度的能力有关的基因。Trpm 8编码存在于冷感觉神经元的质膜上的蛋白质，其属于瞬时受体电位（TRP）通道家族。最近，我们已经确定了一种新的感觉通道，对较冷的温度做出反应，ANKTM 1。ANTKM 1与TRPM 8有较远的亲缘关系，是TRP家族中六个感知温度的成员之一。当外部温度达到临界阈值时，冷激活的TRP通道允许带正电荷的离子进入细胞。我们希望更多地了解这个激活过程。最根本的是，这些通道如何在分子水平上感知寒冷的温度？TRP通道对热刺激的反应机制可能比经典配体门控通道的反应机制更为新颖。最后，我们将询问这些通道是否需要用于体内冷检测和疼痛感觉。