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Potentiation of Fc∈ Receptor I–Activated Ca(2+) Current (I(CRAC)) by Cholera Toxin: Possible Mediation by Adp Ribosylation Factor

Antigen-evoked influx of extracellular Ca(2+) into mast cells may occur via store-operated Ca(2+) channels called calcium release–activated calcium (CRAC) channels. In mast cells of the rat basophilic leukemia cell line (RBL-2H3), cholera toxin (CT) potentiates antigen-driven uptake of (45)Ca(2+) th...

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Autores principales: McCloskey, Michael A., Zhang, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3207143/
https://www.ncbi.nlm.nih.gov/pubmed/10629224
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author McCloskey, Michael A.
Zhang, Lei
author_facet McCloskey, Michael A.
Zhang, Lei
author_sort McCloskey, Michael A.
collection PubMed
description Antigen-evoked influx of extracellular Ca(2+) into mast cells may occur via store-operated Ca(2+) channels called calcium release–activated calcium (CRAC) channels. In mast cells of the rat basophilic leukemia cell line (RBL-2H3), cholera toxin (CT) potentiates antigen-driven uptake of (45)Ca(2+) through cAMP-independent means. Here, we have used perforated patch clamp recording at physiological temperature to test whether cholera toxin or its substrate, Gs, directly modulates the activity of CRAC channels. Cholera toxin dramatically amplified (two- to fourfold) the Ca(2)+ release–activated Ca(2+) current (I(CRAC)) elicited by suboptimal concentrations of antigen, without itself inducing I(CRAC), and this enhancement was not mimicked by cAMP elevation. In contrast, cholera toxin did not affect the induction of I(CRAC) by thapsigargin, an inhibitor of organelle Ca(2+) pumps, or by intracellular dialysis with low Ca(2+) pipette solutions. Thus, the activity of CRAC channels is not directly controlled by cholera toxin or Gsα. Nor was the potentiation of I(CRAC) due to enhancement of phosphoinositide hydrolysis or calcium release. Because Gs and the A subunit of cholera toxin bind to ADP ribosylation factor (ARF) and could modulate its activity, we tested the sensitivity of antigen-evoked I(CRAC) to brefeldin A, an inhibitor of ARF-dependent functions, including vesicle transport. Brefeldin A blocked the enhancement of antigen-evoked I(CRAC) without inhibiting ADP ribosylation of Gsα, but it did not affect I(CRAC) induced by suboptimal antigen or by thapsigargin. These data provide new evidence that CRAC channels are a major route for Fc∈ receptor I–triggered Ca(2+) influx, and they suggest that ARF may modulate the induction of I(CRAC) by antigen.
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spelling pubmed-32071432011-11-03 Potentiation of Fc∈ Receptor I–Activated Ca(2+) Current (I(CRAC)) by Cholera Toxin: Possible Mediation by Adp Ribosylation Factor McCloskey, Michael A. Zhang, Lei J Cell Biol Original Article Antigen-evoked influx of extracellular Ca(2+) into mast cells may occur via store-operated Ca(2+) channels called calcium release–activated calcium (CRAC) channels. In mast cells of the rat basophilic leukemia cell line (RBL-2H3), cholera toxin (CT) potentiates antigen-driven uptake of (45)Ca(2+) through cAMP-independent means. Here, we have used perforated patch clamp recording at physiological temperature to test whether cholera toxin or its substrate, Gs, directly modulates the activity of CRAC channels. Cholera toxin dramatically amplified (two- to fourfold) the Ca(2)+ release–activated Ca(2+) current (I(CRAC)) elicited by suboptimal concentrations of antigen, without itself inducing I(CRAC), and this enhancement was not mimicked by cAMP elevation. In contrast, cholera toxin did not affect the induction of I(CRAC) by thapsigargin, an inhibitor of organelle Ca(2+) pumps, or by intracellular dialysis with low Ca(2+) pipette solutions. Thus, the activity of CRAC channels is not directly controlled by cholera toxin or Gsα. Nor was the potentiation of I(CRAC) due to enhancement of phosphoinositide hydrolysis or calcium release. Because Gs and the A subunit of cholera toxin bind to ADP ribosylation factor (ARF) and could modulate its activity, we tested the sensitivity of antigen-evoked I(CRAC) to brefeldin A, an inhibitor of ARF-dependent functions, including vesicle transport. Brefeldin A blocked the enhancement of antigen-evoked I(CRAC) without inhibiting ADP ribosylation of Gsα, but it did not affect I(CRAC) induced by suboptimal antigen or by thapsigargin. These data provide new evidence that CRAC channels are a major route for Fc∈ receptor I–triggered Ca(2+) influx, and they suggest that ARF may modulate the induction of I(CRAC) by antigen. The Rockefeller University Press 2000-01-10 /pmc/articles/PMC3207143/ /pubmed/10629224 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
McCloskey, Michael A.
Zhang, Lei
Potentiation of Fc∈ Receptor I–Activated Ca(2+) Current (I(CRAC)) by Cholera Toxin: Possible Mediation by Adp Ribosylation Factor
title Potentiation of Fc∈ Receptor I–Activated Ca(2+) Current (I(CRAC)) by Cholera Toxin: Possible Mediation by Adp Ribosylation Factor
title_full Potentiation of Fc∈ Receptor I–Activated Ca(2+) Current (I(CRAC)) by Cholera Toxin: Possible Mediation by Adp Ribosylation Factor
title_fullStr Potentiation of Fc∈ Receptor I–Activated Ca(2+) Current (I(CRAC)) by Cholera Toxin: Possible Mediation by Adp Ribosylation Factor
title_full_unstemmed Potentiation of Fc∈ Receptor I–Activated Ca(2+) Current (I(CRAC)) by Cholera Toxin: Possible Mediation by Adp Ribosylation Factor
title_short Potentiation of Fc∈ Receptor I–Activated Ca(2+) Current (I(CRAC)) by Cholera Toxin: Possible Mediation by Adp Ribosylation Factor
title_sort potentiation of fc∈ receptor i–activated ca(2+) current (i(crac)) by cholera toxin: possible mediation by adp ribosylation factor
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3207143/
https://www.ncbi.nlm.nih.gov/pubmed/10629224
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