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

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

Stable Identifier

R-HSA-8941543

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane, extracellular region

ReviewStatus

5/5

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

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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 Jentsch, TJ, Lutter, D, Planells-Cases, R, Ullrich, F, Voss, FK	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, Dubin, AE, Mathur, J, Tu, B, Reddy, K, Miraglia, LJ, Reinhardt, J, Orth, AP, Patapoutian, A	Cell	2014
26824658	LRRC8 Proteins Form Volume-Regulated Anion Channels that Sense Ionic Strength Syeda, R, Qiu, Z, Dubin, AE, Murthy, SE, Florendo, MN, Mason, DE, Mathur, J, Cahalan, SM, Peters, EC, Montal, M, Patapoutian, A	Cell	2016
24790029	Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC Voss, FK, Ullrich, F, Münch, J, Lazarow, K, Lutter, D, Mah, N, Andrade-Navarro, MA, von Kries, JP, Stauber, T, Jentsch, TJ	Science	2014