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A link of Ca(2+ )to cAMP oscillations in Dictyostelium: the calmodulin antagonist W-7 potentiates cAMP relay and transiently inhibits the acidic Ca(2+)-store
BACKGROUND: During early differentiation of Dictyostelium the attractant cAMP is released periodically to induce aggregation of the cells. Here we pursue the question whether pulsatile cAMP signaling is coupled to a basic Ca(2+)-oscillation. RESULTS: We found that the calmodulin antagonist W-7 trans...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2004
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC419698/ https://www.ncbi.nlm.nih.gov/pubmed/15147588 http://dx.doi.org/10.1186/1471-213X-4-7 |
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author | Malchow, Dieter Lusche, Daniel F Schlatterer, Christina |
author_facet | Malchow, Dieter Lusche, Daniel F Schlatterer, Christina |
author_sort | Malchow, Dieter |
collection | PubMed |
description | BACKGROUND: During early differentiation of Dictyostelium the attractant cAMP is released periodically to induce aggregation of the cells. Here we pursue the question whether pulsatile cAMP signaling is coupled to a basic Ca(2+)-oscillation. RESULTS: We found that the calmodulin antagonist W-7 transiently enhanced cAMP spikes. We show that W-7 acts on an acidic Ca(2+)-store: it abolished ATP-dependent vesicular acidification, inhibited V-type H(+)ATPase activity more potently than the weaker antagonist W-5 and caused vesicular Ca(2+)-leakage. Concanamycin A, an inhibitor of the V-type H(+)-pump, blocked the Ca(2+)-leakage elicited by W-7 as well as cAMP-oscillations in the presence of W-7. Concanamycin A caused an increase of the cytosolic Ca(2+)-concentration whereas W-7 did not. In case of the latter, Ca(2+ )was secreted by the cells. In accord with our hypothesis that the link from Ca(2+ )to cAMP synthesis is mediated by a Ca(2+)-dependent phospholipase C we found that W-7 was not active in the phospholipase C knockout mutant. CONCLUSION: We conclude that the potentiation of cAMP relay by W-7 is due to a transient inhibition of the acidic Ca(2+)-store. The inhibition of the proton pump by W-7 causes a leakage of Ca(2+ )that indirectly stimulates adenylyl cyclase activity via phospholipase C. |
format | Text |
id | pubmed-419698 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-4196982004-05-30 A link of Ca(2+ )to cAMP oscillations in Dictyostelium: the calmodulin antagonist W-7 potentiates cAMP relay and transiently inhibits the acidic Ca(2+)-store Malchow, Dieter Lusche, Daniel F Schlatterer, Christina BMC Dev Biol Research Article BACKGROUND: During early differentiation of Dictyostelium the attractant cAMP is released periodically to induce aggregation of the cells. Here we pursue the question whether pulsatile cAMP signaling is coupled to a basic Ca(2+)-oscillation. RESULTS: We found that the calmodulin antagonist W-7 transiently enhanced cAMP spikes. We show that W-7 acts on an acidic Ca(2+)-store: it abolished ATP-dependent vesicular acidification, inhibited V-type H(+)ATPase activity more potently than the weaker antagonist W-5 and caused vesicular Ca(2+)-leakage. Concanamycin A, an inhibitor of the V-type H(+)-pump, blocked the Ca(2+)-leakage elicited by W-7 as well as cAMP-oscillations in the presence of W-7. Concanamycin A caused an increase of the cytosolic Ca(2+)-concentration whereas W-7 did not. In case of the latter, Ca(2+ )was secreted by the cells. In accord with our hypothesis that the link from Ca(2+ )to cAMP synthesis is mediated by a Ca(2+)-dependent phospholipase C we found that W-7 was not active in the phospholipase C knockout mutant. CONCLUSION: We conclude that the potentiation of cAMP relay by W-7 is due to a transient inhibition of the acidic Ca(2+)-store. The inhibition of the proton pump by W-7 causes a leakage of Ca(2+ )that indirectly stimulates adenylyl cyclase activity via phospholipase C. BioMed Central 2004-05-17 /pmc/articles/PMC419698/ /pubmed/15147588 http://dx.doi.org/10.1186/1471-213X-4-7 Text en Copyright © 2004 Malchow et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. |
spellingShingle | Research Article Malchow, Dieter Lusche, Daniel F Schlatterer, Christina A link of Ca(2+ )to cAMP oscillations in Dictyostelium: the calmodulin antagonist W-7 potentiates cAMP relay and transiently inhibits the acidic Ca(2+)-store |
title | A link of Ca(2+ )to cAMP oscillations in Dictyostelium: the calmodulin antagonist W-7 potentiates cAMP relay and transiently inhibits the acidic Ca(2+)-store |
title_full | A link of Ca(2+ )to cAMP oscillations in Dictyostelium: the calmodulin antagonist W-7 potentiates cAMP relay and transiently inhibits the acidic Ca(2+)-store |
title_fullStr | A link of Ca(2+ )to cAMP oscillations in Dictyostelium: the calmodulin antagonist W-7 potentiates cAMP relay and transiently inhibits the acidic Ca(2+)-store |
title_full_unstemmed | A link of Ca(2+ )to cAMP oscillations in Dictyostelium: the calmodulin antagonist W-7 potentiates cAMP relay and transiently inhibits the acidic Ca(2+)-store |
title_short | A link of Ca(2+ )to cAMP oscillations in Dictyostelium: the calmodulin antagonist W-7 potentiates cAMP relay and transiently inhibits the acidic Ca(2+)-store |
title_sort | link of ca(2+ )to camp oscillations in dictyostelium: the calmodulin antagonist w-7 potentiates camp relay and transiently inhibits the acidic ca(2+)-store |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC419698/ https://www.ncbi.nlm.nih.gov/pubmed/15147588 http://dx.doi.org/10.1186/1471-213X-4-7 |
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