Physiological Functions of the Volume-Regulated Anion Channel VRAC/LRRC8 and the Proton-Activated Chloride Channel ASOR/TMEM206.

Autor:	Kostritskaia Y; Institute for Molecular Medicine, MSH Medical School Hamburg, Hamburg, Germany., Klüssendorf M; Institute for Molecular Medicine, MSH Medical School Hamburg, Hamburg, Germany., Pan YE; Institute for Molecular Medicine, MSH Medical School Hamburg, Hamburg, Germany., Hassani Nia F; Institute for Molecular Medicine, MSH Medical School Hamburg, Hamburg, Germany., Kostova S; Institute for Molecular Medicine, MSH Medical School Hamburg, Hamburg, Germany., Stauber T; Institute for Molecular Medicine, MSH Medical School Hamburg, Hamburg, Germany. tobias.stauber@medicalschool-hamburg.de.
Jazyk:	angličtina
Zdroj:	Handbook of experimental pharmacology [Handb Exp Pharmacol] 2024; Vol. 283, pp. 181-218.
DOI:	10.1007/164_2023_673
Abstrakt:	Volume-regulated anion channels (VRACs) and the acid-sensitive outwardly rectifying anion channel (ASOR) mediate flux of chloride and small organic anions. Although known for a long time, they were only recently identified at the molecular level. VRACs are heteromers consisting of LRRC8 proteins A to E. Combining the essential LRRC8A with different LRRC8 paralogues changes key properties of VRAC such as conductance or substrate selectivity, which is how VRACs are involved in multiple physiological functions including regulatory volume decrease, cell proliferation and migration, cell death, purinergic signalling, fat and glucose metabolism, insulin signalling, and spermiogenesis. VRACs are also involved in pathological conditions, such as the neurotoxic release of glutamate and aspartate. Certain VRACs are also permeable to larger, organic anions, including antibiotics and anti-cancer drugs, making them an interesting therapeutic target. ASOR, also named proton-activated chloride channel (PAC), is formed by TMEM206 homotrimers on the plasma membrane and on endosomal compartments where it mediates chloride flux in response to extracytosolic acidification and plays a role in the shrinking and maturation of macropinosomes. ASOR has been shown to underlie neuronal swelling which causes cell death after stroke as well as promoting the metastasis of certain cancers, making them intriguing therapeutic targets as well. (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)
Databáze:	MEDLINE
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