ER-localized bestrophin 1 activates Ca2+-dependent ion channels TMEM16A and SK4 possibly by acting as a counterion channel.
Pflugers Arch
; 459(3): 485-97, 2010 Feb.
Article
en En
| MEDLINE
| ID: mdl-19823864
ABSTRACT
Bestrophins form Ca(2+)-activated Cl(-) channels and regulate intracellular Ca(2+) signaling. We demonstrate that bestrophin 1 is localized in the endoplasmic reticulum (ER), where it interacts with stromal interacting molecule 1, the ER-Ca(2+) sensor. Intracellular Ca(2+) 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 Ca(2+) signaling and activation of Ca(2+)-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 Ca(2+) deposits. hBest1 is, therefore, important for Ca(2+) handling of the ER store and may resemble the long-suspected counterion channel to balance transient membrane potentials occurring through inositol triphosphate (IP(3))-induced Ca(2+) release and store refill. Thus, bestrophin 1 regulates compartmentalized Ca(2+) signaling that plays an essential role in Best macular dystrophy, inflammatory diseases such as cystic fibrosis, as well as proliferation.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Canales de Cloruro
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Retículo Endoplásmico
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Canales de Potasio de Conductancia Intermedia Activados por el Calcio
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Proteínas del Ojo
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Proteínas de la Membrana
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Proteínas de Neoplasias
Límite:
Animals
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Humans
Idioma:
En
Revista:
Pflugers Arch
Año:
2010
Tipo del documento:
Article
País de afiliación:
Alemania