VRAC heteromer transports I-, Cl- from cytosol to extracellular region

Stable Identifier
Reaction [transition]
Homo sapiens
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Maintaining a constant cell volume in response to extracellular or intracellular osmotic changes is critical for cellular homeostasis. The volume-regulated anion channel (VRAC), localised on the plasma membrane, plays a key role in this process. VRAC is proposed to be a heterohexamer composed of an essential subunit, the volume-regulated anion channel subunit LRRC8A (SWELL1) (Qiu et al. 2014, Voss et al. 2014) and any one of four other LRRC8s; LRRC8B, LRRC8C, LRRC8D and LRRC8E (Syeda et al. 2016, Mongin 2016). The resulting diverse hexameric channels that can form are thought to produce diverse physiological roles for VRAC (Jentsch et al. 2016). VRAC mediates the so-called swelling-induced Cl- current (ICl, swell) which is primarily carried by Cl- but can also be other ions and small organic osmolytes. Indeed, VRAC has highest affinity for I- followed by Cl-. It counters cell swelling by causing a regulatory volume decrease (RVD) through ion and osmolyte efflux followed by release of osmotically-obligated water.
Literature References
PubMed ID Title Journal Year
26635246 VRAC: molecular identification as LRRC8 heteromers with differential functions

Planells-Cases, R, Lutter, D, Voss, FK, Jentsch, TJ, Ullrich, F

Pflugers Arch. 2016
26620797 Volume-regulated anion channel--a frenemy within the brain

Mongin, AA

Pflugers Arch. 2016
24725410 SWELL1, a plasma membrane protein, is an essential component of volume-regulated anion channel

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

Cell 2014
26824658 LRRC8 Proteins Form Volume-Regulated Anion Channels that Sense Ionic Strength

Qiu, Z, Dubin, AE, Cahalan, SM, Mason, DE, Patapoutian, A, Peters, EC, Murthy, SE, Syeda, R, Florendo, MN, Montal, M, Mathur, J

Cell 2016
24790029 Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC

Andrade-Navarro, MA, M√ľnch, J, Stauber, T, Mah, N, Lutter, D, von Kries, JP, Jentsch, TJ, Voss, FK, Lazarow, K, Ullrich, F

Science 2014
Catalyst Activity

volume-sensitive anion channel activity of VRAC heteromer [plasma membrane]

Orthologous Events
Cross References
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