Molecular characterization of Sensory Function

描述(申请人提供)：尽管我们通常认为疼痛、温暖或寒冷等感觉是理所当然的，但参与这些过程的分子会对外部世界做出复杂的生物反应，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。有关感知这些刺激的基因仍有很大一部分是未知的。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。使用这些工具，我们最近克隆了第一个与我们感知寒冷温度能力有关的基因。TRPM8编码一种存在于冷敏感神经元质膜上的蛋白质，属于瞬时受体电位(Trp)通道家族。最近，我们发现了一种新的感觉通道，ANKTM1，它对较低的温度做出反应。ANTKM1与TRPM8有较远的亲缘关系，是六个感温色氨酸家族成员之一。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一激活过程。最根本的是，这些通道实际上是如何在分子水平上感知寒冷温度的？与经典的配基门控通道相比，Trp通道对热刺激的反应机制可能完全不同。最后，我们将询问这些通道是否需要在体内进行寒冷检测和痛感。

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.