| Role of bestrophin-1 in store-operated calcium entry in retinal pigment epithelium. | |
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MedLine Citation:
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PMID: 23207577 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The retinal pigment epithelium (RPE) expresses bestrophin-1 where mutant bestrophin cause retinal degenerations. Overexpression of bestrophin-1 demonstrated Ca(2+)-dependent Cl(-) channel function, whereas the RPE in bestrophin-1 knockout or mutant bestrophin-1 knock-in mice showed no change in Cl(-) conductance. To account for these apparently mutually exclusive findings, we investigated the function of endogenously expressed bestrophin-1 in a short-time RPE cell culture system by means of immunocytochemistry, Ca(2+) imaging, and siRNA knockdown. Immunocytochemical quantification of bestrophin-1 localization demonstrated 2.5 times higher co-localization with the endoplasmic reticulum (ER) Ca(2+)-sensor protein, Stim-1, than with the membrane protein β-catenin, implicating it in store-operated Ca(2+) entry (SOCE). Ca(2+) release from ER stores under extracellular Ca(2+)-free conditions using thapsigargin (1 μM) to inhibit endoplasmic Ca(2+) ATPase (SERCA) followed by re-adjustment of extracellular Ca(2+) to physiological levels activated SOCE, which was insensitive to the blocker of numerous transient receptor potential channels and voltage-dependent Ca(2+) channels SKF96563 (1 μM). SOCE was augmented at 5 μM and inhibited at 75 μM by 2-aminoethoxydiphenyl borate which indicates the involvement Orai-1 channels. In confirmation, SOCE was decreased by siRNA knockdown of Orai-1 expression. SOCE amplitude was strongly reduced by siRNA knockdown of bestrophin-1 expression, which was due to neither changes in Stim-1/Orai-1 expression nor Stim-1/bestrophin-1 interaction. The amount of Ca(2+) released by SERCA inhibition was reduced after siRNA knockdown of bestrophin-1, but not of Orai-1. In conclusion we found that a proportion of bestrophin-1 is functionally localized to ER Ca(2+) stores where it influences the amount of Ca(2+) and therefore Ca(2+) signals which result from activation of Orai-1 via Stim-1. |
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Authors:
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Néstor Más Gómez; Ernst R Tamm; Olaf Strauβ |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-12-4 |
Journal Detail:
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Title: Pflugers Archiv : European journal of physiology Volume: - ISSN: 1432-2013 ISO Abbreviation: Pflugers Arch. Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0154720 Medline TA: Pflugers Arch Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Experimental Ophthalmology, Eye Hospital, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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