SWELL1, a plasma membrane protein, is an essential component of volume-regulated anion channel.

Abstract:

:Maintenance of a constant cell volume in response to extracellular or intracellular osmotic changes is critical for cellular homeostasis. Activation of a ubiquitous volume-regulated anion channel (VRAC) plays a key role in this process; however, its molecular identity in vertebrates remains unknown. Here, we used a cell-based fluorescence assay and performed a genome-wide RNAi screen to find components of VRAC. We identified SWELL1 (LRRC8A), a member of a four-transmembrane protein family with unknown function, as essential for hypotonicity-induced iodide influx. SWELL1 is localized to the plasma membrane, and its knockdown dramatically reduces endogenous VRAC currents and regulatory cell volume decrease in various cell types. Furthermore, point mutations in SWELL1 cause a significant change in VRAC anion selectivity, demonstrating that SWELL1 is an essential VRAC component. These findings enable further molecular characterization of the VRAC channel complex and genetic studies for understanding the function of VRAC in normal physiology and disease.

journal_name

Cell

journal_title

Cell

authors

Qiu Z,Dubin AE,Mathur J,Tu B,Reddy K,Miraglia LJ,Reinhardt J,Orth AP,Patapoutian A

doi

10.1016/j.cell.2014.03.024

subject

Has Abstract

pub_date

2014-04-10 00:00:00

pages

447-458

issue

2

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(14)00358-4

journal_volume

157

pub_type

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