Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Malchow, Dieter, Lusche, Daniel F, Schlatterer, Christina
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2004
Materias:
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
_version_ 1782121443484499968
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
work_keys_str_mv AT malchowdieter alinkofca2tocamposcillationsindictyosteliumthecalmodulinantagonistw7potentiatescamprelayandtransientlyinhibitstheacidicca2store
AT luschedanielf alinkofca2tocamposcillationsindictyosteliumthecalmodulinantagonistw7potentiatescamprelayandtransientlyinhibitstheacidicca2store
AT schlattererchristina alinkofca2tocamposcillationsindictyosteliumthecalmodulinantagonistw7potentiatescamprelayandtransientlyinhibitstheacidicca2store
AT malchowdieter linkofca2tocamposcillationsindictyosteliumthecalmodulinantagonistw7potentiatescamprelayandtransientlyinhibitstheacidicca2store
AT luschedanielf linkofca2tocamposcillationsindictyosteliumthecalmodulinantagonistw7potentiatescamprelayandtransientlyinhibitstheacidicca2store
AT schlattererchristina linkofca2tocamposcillationsindictyosteliumthecalmodulinantagonistw7potentiatescamprelayandtransientlyinhibitstheacidicca2store