Mechanisms of force sensing in the nervous system

神经系统中的力传感机制

基本信息

批准号：
10308074
负责人：
Ardem Patapoutian
金额：
$ 67.73万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-12-15 至 2025-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10308074
关键词：
Cations Functional disorder Genomic approach Hearing Interoception Ion Channel Lung Mechanics Mediating Molecular Nervous system structure Organ Pain Physiological Physiology Piezo 1 ion channel Piezo 2 ion channel Play Process Proprioception Role Satiation Sensory Smell Perception Stretching System Taste Perception Touch sensation Vision functional genomics high throughput screening mechanical force mechanical stimulus mechanotransduction pain perception receptor sensor sensory system therapeutic target

Cations Functional disorder Genomic approach Hearing Interoception Ion Channel Lung Mechanics Mediating Molecular Nervous system structure Organ Pain Physiological Physiology Piezo 1 ion channel Piezo 2 ion channel Play Process Proprioception Role Satiation Sensory Smell Perception Stretching System Taste Perception Touch sensation Vision functional genomics high throughput screening mechanical force mechanical stimulus mechanotransduction pain perception receptor sensor sensory system therapeutic target

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项目摘要

Unlike sight, taste and smell, mechanical senses extend beyond a single sensory organ, and encompass processes as diverse as hearing, somatosensation, and interoception. Despite their physiological importance, the molecular identity of mechanotransduction channels is largely unknown. Our lab discovered the first vertebrate mechanically-gated cation channels, Piezo1 and Piezo2, and have shown that Piezo2 plays a critical role in detecting touch, proprioception and lung stretch, but not noxious mechanical stimuli. However, big questions remain: what other mechanosensory systems depend on Piezos, and what is the identity of the remaining noxious mechanosensors? We will explore the role of Piezo2 in various forms of internal-organ mechanotransduction (interoception), including satiety and baroreception - processes crucial for normal physiology and pathophysiology. Beyond Piezo2, unknown mechanosensors mediate the transduction of noxious mechanical forces leading to the perception of pain, and are anticipated to be important therapeutic targets. We will use high-throughput screens and functional genomics approaches to find these receptors. Identifying these elusive sensors will break open the pain field, as Piezo2 has done for touch.

与视觉，味道和气味不同，机械感官超越了单个感觉器官，并且涵盖了听力，节感和感觉的多样化过程。尽管它们的生理重要性，但机械传输通道的分子身份在很大程度上尚不清楚。我们的实验室发现了第一个脊椎动物机械门控的阳离子通道Piezo1和Piezo2，并表明Piezo2在检测触摸，本体感受和肺伸展方面起着至关重要的作用，但不是有害的机械刺激。但是，仍然存在很大的问题：其他哪些机械感觉系统取决于压电，其余有害机械传感器的身份是什么？我们将探讨压电2在各种形式的内部器官机械转导（Interoception）中的作用，包括饱腹感和压力感受 - 对正常生理学和病理生理学至关重要。除压电2之外，未知的机械传感器可以介导导致疼痛感知的有害机械力的转导，并预计将是重要的治疗靶标。我们将使用高通量筛选和功能基因组学方法来查找这些受体。像Piezo2为触摸所做的那样，识别这些难以捉摸的传感器将破坏疼痛场。