Mechanosensitive gating of CFTR
Publication in refereed journal

香港中文大學研究人員

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摘要Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion and intracellular ligand-gated channel associated with cystic fibrosis, a lethal genetic disorder common among Caucasians(1). Here we show that CFTR is robustly activated by membrane stretch induced by negative pressures as small as 5 mmHg at the single-channel, cellular and tissue levels. Stretch increased the product of the number of channels present and probability of being open (NPo), and also increased the unitary conductance of CFTR in cell-attached membrane patches. CFTR stretch-mediated activation appears to be an intrinsic property independent of cytosolic factors and kinase signalling. CFTR stretch-mediated activation resulted in chloride transport in Calu-3 human airway epithelial cells and mouse intestinal tissues. Our study has revealed an unexpected function of CFTR in mechanosensing, in addition to its roles as a ligand-gated anion channel(1) and a regulator of other membrane transporters(2), demonstrating for the first time a mechanosensitive anion channel with a clearly defined molecular identity. Given that CFTR is often found in mechanically dynamic environments, its mechanosensitivity has important physiological implications in epithelial ion transport and cell volume regulation in vivo.
著者Zhang WK, Wang D, Duan YY, Loy MMT, Chan HC, Huang PB
期刊名稱Nature Cell Biology
出版年份2010
月份5
日期1
卷號12
期次5
出版社Nature Publishing Group
頁次507 - U214
國際標準期刊號1465-7392
電子國際標準期刊號1476-4679
語言英式英語
Web of Science 學科類別Cell Biology; CELL BIOLOGY

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