Barro-Soria, Rene and Aldehni, Fadi and Almaca, Joana and Witzgall, Ralph and Schreiber, Rainer and Kunzelmann, Karl (2010) ER-localized bestrophin 1 activates Ca2+-dependent ion channels TMEM16A and SK4 possibly by acting as a counterion channel. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 459 (3). pp. 485-497. ISSN 0031-6768, 1432-2013
Full text not available from this repository. (Request a copy)Abstract
Bestrophins form Ca2+-activated Cl- channels and regulate intracellular Ca2+ signaling. We demonstrate that bestrophin 1 is localized in the endoplasmic reticulum (ER), where it interacts with stromal interacting molecule 1, the ER-Ca2+ sensor. Intracellular Ca2+ transients elicited by stimulation of purinergic P2Y(2) receptors in HEK293 cells were augmented by hBest1. The p21-activated protein kinase Pak2 was found to phosphorylate hBest1, thereby enhancing Ca2+ signaling and activation of Ca2+-dependent Cl- (TMEM16A) and K+ (SK4) channels. Lack of bestrophin 1 expression in respiratory epithelial cells of mBest1 knockout mice caused expansion of ER cisterns and induced Ca2+ deposits. hBest1 is, therefore, important for Ca2+ handling of the ER store and may resemble the long-suspected counterion channel to balance transient membrane potentials occurring through inositol triphosphate (IP3)-induced Ca2+ release and store refill. Thus, bestrophin 1 regulates compartmentalized Ca2+ signaling that plays an essential role in Best macular dystrophy, inflammatory diseases such as cystic fibrosis, as well as proliferation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ENDOPLASMIC-RETICULUM; SARCOPLASMIC-RETICULUM; CHLORIDE CONDUCTANCE; CA2+; MEMBRANE; MECHANISMS; EXPRESSION; Bestrophin; Ca2+-activated Cl- currents; CaCC; Ca2+-activated K+ currents; SK4; TMEM16A; Pak2; Purinergic receptors; Endoplasmic reticulum; ER; Ca2+ store |
| 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: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Aug 2020 09:14 |
| Last Modified: | 10 Aug 2020 09:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25256 |
Actions (login required)
 |
View Item |
