More than just a pressure release valve: physiological roles of volume-regulated LRRC8 anion channels.

More than just a pressure release valve: physiological roles of volume-regulated LRRC8 anion channels. Biol Chem. 2019 May 01;: Authors: Chen L, König B, Liu T, Pervaiz S, Razzaque YS, Stauber T Abstract The volume-regulated anion channel (VRAC) is a key player in volume regulation of vertebrate cells. This ubiquitously expressed channel opens upon osmotic cell swelling and potentially other cues and releases chloride and organic osmolytes, which contributes to regulatory volume decrease (RVD). A plethora of studies proposed a wide range of physiological roles for VRAC beyond volume regulation including cell proliferation, differentiation and migration, apoptosis, intercellular communication by direct release of signaling molecules and by supporting exocytosis of insulin. VRAC was additionally implicated in pathological states such as cancer therapy resistance and excitotoxicity under ischemic conditions. Following extensive investigations, five years ago leucine-rich repeatcontaining family 8 (LRRC8) heteromers containing LRRC8A were identified as the poreforming components of VRAC. Since then, molecular biological approaches have allowed further insight into the biophysical properties and structure of VRAC. Heterologous expression, siRNA mediated downregulation and genome editing in cells, as well as the use of animal models have enabled the assessment of the proposed physiological roles, together with the identification of new fu...
Source: Biological Chemistry - Category: Chemistry Tags: Biol Chem Source Type: research