Functional assembly and purinergic activation of bestrophins.

Pflügers Archiv : European journal of physiology
Vladimir M MilenkovicKarl Kunzelmann

Abstract

Proteins of the bestrophin family produce Ca(2+)-activated Cl(-) currents and regulate voltage-gated Ca(2+) channels. Bestrophin 1 was first identified in the retinal pigment epithelium. Four human paralogs (hBest1-hBest4) exist, and for some bestrophins, dimeric and heterotetrameric structures have been proposed. Here, we demonstrate that hBest1-hBest4 induce Cl(-) conductances of different amplitudes when expressed in HEK293 cells and when activated through purinergic stimulation. hBest1 mutants that are known to cause autosomal dominant macular dystrophy (Best disease) did not produce a Cl(-) current. Bestrophins were colocalized and showed molecular and functional interaction in HEK293 cells, overexpressing hBest1 and hBest2 or hBest4. Interaction was confirmed in airway epithelial cells coexpressing endogenous bestrophins. A fraction of hBest2 and hBest4 was expressed in the membrane, while most of hBest1 was found in the endoplasmic reticulum. Nevertheless, hBest1 has a clear role for the adenosine triphosphate (ATP; or uridine triphosphate)-induced Cl(-) current in both HEK293 and Calu-3 cells. Since native epithelial tissues typically express several bestrophin paralogs, these proteins may exist as heterooligomeric stru...Continue Reading

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Citations

Oct 14, 2009·Pflügers Archiv : European journal of physiology·René Barro-SoriaKarl Kunzelmann
Apr 23, 2010·Pflügers Archiv : European journal of physiology·Rudgar NeussertOlaf Strauss
Aug 15, 2009·The Journal of Biological Chemistry·Jiraporn OusingsawatKarl Kunzelmann
Apr 19, 2011·Cardiovascular Research·Torbjoern BroeggerVladimir V Matchkov
May 28, 2009·Journal of the American Society of Nephrology : JASN·Fadi AldehniKarl Kunzelmann
Apr 13, 2010·Ophthalmology·Judith C BooijCaroline C W Klaver
Sep 29, 2009·Cell Calcium·Karl KunzelmannRainer Schreiber
Aug 3, 2011·Journal of Cellular Physiology·Jiraporn OusingsawatKarl Kunzelmann
Dec 18, 2013·Ophthalmic Genetics·Caroline PasquayMarkus N Preising
Aug 16, 2016·Disease Models & Mechanisms·Carolina UggentiForbes D Manson
Sep 1, 2011·Journal of Cell Science·Vladimir M MilenkovicOlaf Strauss

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