Molecular Mechanism of Mechanosensation

机械感觉的分子机制

• 批准号: 8572786
• 负责人: Scott B Hansen
• 金额: $ 283.5万
• 依托单位: SCRIPPS FLORIDA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8572786
• 关键词: Cells; Esthesia; Eukaryota; Hearing; Human; Ion Channel; Lipids; Mammals; Mechanics; Modeling; Molecular; Pain; Perception; Play; Role; Sensory; Therapeutic Intervention; Tissues; Touch sensation; hearing impairment

DESCRIPTION (provided by applicant): Mechanosensation provides two of the 5 fundamental senses integral to human sensation-touch and hearing. Surprisingly, the seemingly simple sense of "touch" lacks a satisfactory molecular description in eukaryotes. The question remains: How do molecules in a cell sense and transduce mechanical force in tissue? In mammals ion channels are believed to play a role in mechanosensation; however, studies of mechanosensitive channels have failed to identify a clear structural domain or feature responsible for sensing mechanical force. Absent a clear mechanism for mechanosensation in humans, testable hypotheses are needed to arrive at a correct model. This proposal presents an argument that lipid interactions with ion channels are important to mechano sensation. Forming a molecular description of force transduction will, one, complete our understanding of sensory perception and, two, reveal targets for therapeutic intervention in pain and hearing loss.

描述（由申请人提供）：机械感觉提供了人类感觉不可或缺的 5 种基本感觉中的两种——触觉和听觉。令人惊讶的是，看似简单的“触觉”在真核生物中缺乏令人满意的分子描述。问题仍然是：细胞中的分子如何感知和转换组织中的机械力？在哺乳动物中，离子通道被认为在机械感觉中发挥作用。然而，机械敏感通道的研究未能确定负责感测机械力的明确结构域或特征。由于缺乏明确的人类机械感觉机制，需要可测试的假设才能得出正确的模型。该提案提出了一个论点，即脂质与离子通道的相互作用对于机械感觉很重要。形成力传导的分子描述，一是完善我们对感觉知觉的理解，二是揭示疼痛和听力损失治疗干预的目标。

项目成果

Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D.

脂筏的动力学破坏是磷脂酶 D 的机械传感器。

• 发表时间: 2016
• 影响因子: 16.6
• 作者: Petersen, E Nicholas;Chung, Hae;Nayebosadri, Arman;Hansen, Scott B
• 通讯作者: Hansen, Scott B

Lipid agonism: The PIP2 paradigm of ligand-gated ion channels.

脂质激动：配体门控离子通道的 PIP2 范例。

• 发表时间: 2015-05
• 作者: Hansen; Scott B
• 通讯作者: Scott B

A Soluble Fluorescent Binding Assay Reveals PIP2 Antagonism of TREK-1 Channels.

可溶性荧光结合测定揭示了 TREK-1 通道的 PIP2 拮抗作用。

• 发表时间: 2017-08-08
• 影响因子: 8.8
• 作者: Cabanos, Cerrone;Wang, Miao;Han, Xianlin;Hansen, Scott B
• 通讯作者: Hansen, Scott B