Referenced in: none

Automatically associated channels: ClC3 , ClC4 , Slo1

Title: The presence of bestrophin-1 modulates the Ca(2+) recruitment from Ca (2+) stores in the ER.

Authors: Rudgar Neussert, Claudia Müller, Vladimir M Milenkovic, Olaf Strauss

Journal, date & volume: , 2010 Apr 22 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20411394

Abstract
Bestrophin-1, mainly analyzed in overexpression experiments, functions as Ca(2+)-dependent Cl(-) channel. Analysis of endogenously expressed bestrophin-1 suggested an influence on intracellular Ca(2+). The aim of the study is to analyze the influence of endogenously expressed bestrophin-1 on Ca(2+) homeostasis. Primary cultures of retinal pigment epithelial (RPE) cells were established from wild-type and bestrophin-1-deficient mice. Intracellular free Ca(2+) ([Ca(2+)](i)) was recorded by Ca(2+) imaging; through immunocytochemistry and differential centrifugation, subcellular localization of bestrophin-1 was analyzed. RPE cells of bestrophin-1-deficient mice showed higher levels of resting [Ca(2+)](i) than cells from wild-type mice. In cells from knockout mice and wild-type mice, ATP led to increases in [Ca(2+)](i) subsequent to phospholipase C activation. ATP-induced Ca(2+) in bestrophin-1-deficient mice rose faster and decayed slower. In cells from wild-type mice, ATP led to [Ca(2+)](i) increase via depletion of Ca(2+) from thapsigargin-sensitive stores. In cells from bestrophin-1-deficient mice, ATP-dependent increase in [Ca(2+)](i) resulted in 40% of cells from depletion of bafilomycin-sensitive and in 60% from thapsigargin-sensitive Ca(2+) stores. After differential centrifugation, bestrophin-1 was found in fractions enriched of ClC-3 Cl channel and myosin-7A. Co-localization analysis of bestrophin-1, with beta-catenin or pan-cadherin, in fresh sections of porcine retina, revealed bestrophin-1 in the basolateral membrane. A portion of endogenously expressed bestrophin-1,localized in the endoplasmic reticulum, influenced uptake of Ca(2+) into Ca(2+) stores. Therefore, bestrophin-1 possibly conducts Cl(-) as counter ion for Ca(2+) uptake into cytosolic Ca(2+) stores.