Role of the Ca2+-activated Cl- channels bestrophin and anoctamin in epithelial cells

Kunzelmann, Karl and Kongsuphol, Patthara and Chootip, Krongkarn and Toledo, Caio and Martins, Joana R. and Almaca, Joana and Tian, Yuemin and Witzgall, Ralph and Ousingsawat, Jiraporn and Schreiber, Rainer (2011) Role of the Ca2+-activated Cl- channels bestrophin and anoctamin in epithelial cells. BIOLOGICAL CHEMISTRY, 392 (1-2). pp. 125-134. ISSN 1431-6730

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Abstract

Two families of proteins, the bestrophins (Best) and the recently cloned TMEM16 proteins (anoctamin, Ano), recapitulate properties of Ca2+-activated Cl- currents. Best1 is strongly expressed in the retinal pigment epithelium and could have a function as a Ca2+-activated Cl- channel as well as a regulator of Ca2+ signaling. It is also present at much lower levels in other cell types including epithelial cells, where it regulates plasma membrane localized Cl- channels by controlling intracellular Ca2+ levels. Best1 interacts with important Ca2+-signaling proteins such as STIM1 and can interact directly with other Ca2+-activated Cl- channels such as TMEM16A. Best1 is detected in the endoplasmic reticulum (ER) where it shapes the dynamic ER structure and regulates cell proliferation, which could be important for renal cystogenesis. Ca2+-activated Cl- channels of the anoctamin family (TMEM16A) show biophysical and pharmacological properties that are typical for endogenous Ca2+-dependent Cl- channels. TMEM16 proteins are abundantly expressed and many reports demonstrate their physiological importance in epithelial as well as non-epithelial cells. These channels are also activated by cell swelling and can therefore control cell volume, proliferation and apoptosis. To fully understand the function and regulation of Ca2+-activated Cl- currents, it is necessary to appreciate that Best1 and TMEM16A are embedded in a protein network and that they probably operate in functional microdomains.

Item Type: Article
Uncontrolled Keywords: VITELLIFORM MACULAR DYSTROPHY; SMOOTH-MUSCLE-CELLS; ACTIVATED CHLORIDE CHANNEL; GLAND ACINAR-CELLS; FUNCTIONAL-PROPERTIES; INTERSTITIAL-CELLS; BEST-DISEASE; PROTEIN; EXPRESSION; TMEM16A; anoctamin 1; bestrophin; Ca2+-activated Cl- currents (CaCCs); cancer; cystic fibrosis; purinergic receptors; TMEM16A; TMEM16B
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann
Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Molekulare und zelluläre Anatomie > Prof. Dr. Ralph Witzgall
Depositing User: Petra Gürster
Date Deposited: 22 Apr 2020 06:58
Last Modified: 22 Apr 2020 06:58
URI: https://pred.uni-regensburg.de/id/eprint/21493

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