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- W2886177593 abstract "The Volume-Regulated Anion Channel (VRAC) is activated by cell swelling and plays a key role in cell volume regulation. VRAC is ubiquitously expressed in vertebrate cells and also implicated in many other physiological and cellular processes including fluid secretion, glutamate release, membrane potential regulation, cell proliferation, migration, and apoptosis. Although its biophysical properties have been well characterized, the molecular identity of VRAC remained a mystery for almost three decades. The field was transformed by recent discoveries showing that the leucine-rich repeat-containing protein 8A (LRRC8A, also named SWELL1) and its four other homologs form heteromeric VRAC channels. The composition of LRRC8 subunits determines channel properties and substrate selectivity of a large variety of different VRACs. Incorporating purified SWELL1-containing protein complexes into lipid bilayers is sufficient to reconstitute channel activities, a finding that supports the decrease in intracellular ionic strength as the mechanism of VRAC activation during cell swelling. Characterization of Swell1 knockout mice uncovers the important role of VRAC in T cell development, pancreatic β-cell glucose-stimulated insulin secretion, and adipocyte metabolic function. The ability to permeate organic osmolytes and metabolites is a major feature of VRAC. The list of VRAC substrates is expected to grow, now also including some cancer drugs and antibiotics even under non-cell swelling conditions. Therefore, a critical role of VRAC in drug resistance and cell-cell communication is emerging. This review summarizes the exciting recent progress on the structure-function relationship and physiology of VRAC and discusses key future questions to be solved." @default.
- W2886177593 created "2018-08-22" @default.
- W2886177593 creator A5008799139 @default.
- W2886177593 creator A5019984785 @default.
- W2886177593 creator A5027911001 @default.
- W2886177593 creator A5091463065 @default.
- W2886177593 date "2018-01-01" @default.
- W2886177593 modified "2023-10-11" @default.
- W2886177593 title "Molecular Biology and Physiology of Volume-Regulated Anion Channel (VRAC)" @default.
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