Structure Function of Mechanically Activated Ion Channel

机械激活离子通道的结构功能

基本信息

批准号：
8871818
负责人：
Ardem Patapoutian
金额：
$ 41.45万
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：
2012-09-30 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8871818
关键词：
Amino Acids Animals Antibodies Biological Assay Biological Process Blood Vessels C-terminal Caenorhabditis elegans Cardiovascular Diseases Cations Cell Line Cell membrane Cell surface Cells Characteristics Chimera organism Collaborations Complementary DNA Complex Data Disease Electrophysiology (science)Epitopes Esthesia Exhibits Failure Family Future Growth Hearing Homo Ion Channel Ions Kinetics Learning Length Life Link Lipid Bilayers Liposomes Malignant Neoplasms Mammalian Cell Mechanics Medical Methods Molecular Mus Mutagenesis Names Neurons Osteoporosis Pain Pathology Pathway interactions Plants Property Protein Region Proteins RNA Interference Role Ruthenium Red Smooth Muscle Myocytes Stimulus Structure Temperature Testing Tissues Touch sensation Transmembrane Domain Vertebrates Work biological systems biophysical properties cell growth cell type cold temperature dalton deafness inflammatory pain member pressure protein structure reconstitution research study response somatosensory stoichiometry tool

项目摘要

DESCRIPTION (provided by applicant): For sense of touch/pain and hearing, cation channels that are directly activated in response to mechanical forces have been characterized. In addition, many other cell types including vascular smooth muscle cells express such mechanically-activated (MA) cationic currents, and mechanotransduction is implicated in various biological processes and diseases. Remarkably, however, the identity of these ion channels in vertebrates has remained unknown. We recently identified MA cation channel components in vertebrates named Piezo1 and Piezo2. Expressing Piezos in a variety of mammalian cell lines induce large MA cationic currents. Piezos are expressed in a variety of tissues implicated in mechanotransduction. Piezo1 and Piezo2 contain over 24 putative transmembrane domains but do not resemble known ion channels or other protein classes. Many important open questions remain about the structure of these proteins. Here, we hypothesize that Piezo1 oligomerizes to form pore-containing subunits of mechanically-activated ion channels.

描述（由申请人提供）：对于触觉/疼痛感和听觉，已经表征了响应于机械力而直接激活的阳离子通道。此外，包括血管平滑肌细胞在内的许多其他细胞类型表达这种机械激活（MA）阳离子电流，并且机械转导与各种生物过程和疾病有关。然而值得注意的是，脊椎动物中这些离子通道的身份仍然未知。我们最近在脊椎动物中鉴定出 MA 阳离子通道成分，名为 Piezo1 和 Piezo2。在多种哺乳动物细胞系中表达 Piezos 会诱导大的 MA 阳离子电流。压电在与机械转导有关的多种组织中表达。 Piezo1 和 Piezo2 包含超过 24 个假定的跨膜结构域，但与已知的离子通道或其他蛋白质类别不同。关于这些蛋白质的结构仍然存在许多重要的悬而未决的问题。在这里，我们假设 Piezo1 寡聚形成机械激活离子通道的含孔亚基。