Mechanosensitive gating of CFTR

Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in dynamic environments, such as the lung. CFTR is known to be activated by ligand binding. Here, it is also found to be activated by mechanical stretching of cellular membranes. Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion and intracellular ligand-gated channel associated with cystic fibrosis, a lethal genetic disorder common among Caucasians1. 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 channel1 and a regulator of other membrane transporters2, 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.

Cite this article

Zhang, W., Wang, D., Duan, Y. et al. Mechanosensitive gating of CFTR. Nat Cell Biol 12, 507–512 (2010). https://doi.org/10.1038/ncb2053

View full text

>> Full Text:   Mechanosensitive gating of CFTR