Structure Function of Mechanically Activated Ion Channel

机械激活离子通道的结构功能

• 批准号: 8681567
• 负责人: Ardem Patapoutian
• 金额: $ 41.04万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8681567
• 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

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(申请人提供)：对于触觉/疼痛和听觉，已经确定了响应机械力而直接激活的阳离子通道的特征。此外，许多其他类型的细胞，包括血管平滑肌细胞，表达这种机械激活(MA)的阳离子电流，机械转导与各种生物学过程和疾病有关。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发现了MA阳离子通道组分，命名为Piezo1和Piezo2。在多种哺乳动物细胞系中表达Piezos可引起较大的MA阳离子电流。Piezo在与机械转导有关的各种组织中都有表达。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，还有许多重要的悬而未决的问题。在这里，我们假设Piezo1寡聚形成含有孔洞的机械激活离子通道的亚基。