cAMP synthesis and degradation by phagosomes regulate actin assembly and fusion events: consequences for mycobacteria

Απλή σελίδα τεκμηρίου
dc.contributor.authorKalamidas, S. A.en
dc.contributor.authorKuehnel, M. P.en
dc.contributor.authorPeyron, P.en
dc.contributor.authorRybin, V.en
dc.contributor.authorRauch, S.en
dc.contributor.authorKotoulas, O. B.en
dc.contributor.authorHouslay, M.en
dc.contributor.authorHemmings, B. A.en
dc.contributor.authorGutierrez, M. G.en
dc.contributor.authorAnes, E.en
dc.contributor.authorGriffiths, G.en
dc.date.accessioned2015-11-24T19:32:00Z
dc.date.available2015-11-24T19:32:00Z
dc.identifier.issn0021-9533-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/23349
dc.rightsDefault Licence-
dc.subjectActins/*metabolismen
dc.subjectAnimalsen
dc.subject*Cell Fusionen
dc.subjectCyclic AMP/*metabolismen
dc.subjectCyclic AMP-Dependent Protein Kinase RIIalpha Subuniten
dc.subjectCyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/metabolismen
dc.subjectIsoquinolines/metabolismen
dc.subjectLysosomes/metabolismen
dc.subjectMacrophages/cytology/metabolism/microbiologyen
dc.subjectMiceen
dc.subjectMicrospheresen
dc.subjectMycobacterium/cytology/*physiologyen
dc.subjectPhagosomes/*metabolism/ultrastructureen
dc.subjectProtein Kinase Inhibitors/metabolismen
dc.subjectSulfonamides/metabolismen
dc.titlecAMP synthesis and degradation by phagosomes regulate actin assembly and fusion events: consequences for mycobacteriaen
heal.abstractWe showed recently that actin assembly by phagosomal membranes facilitates fusion with late endocytic organelles in macrophages. Moreover, lipids that induced phagosomal actin also stimulated this fusion process. In macrophages infected with pathogenic mycobacteria actin-stimulatory lipids led to an increase in pathogen destruction, whereas inhibitors facilitated their growth. A model was proposed whereby phagosomal membrane actin assembly provides tracks for lysosomes to move towards phagosomes, thereby facilitating fusion. Here, we investigated how cAMP affected phagosomal actin assembly in vitro, and phagosomal actin, acidification and late fusion events in J774 macrophages. Latex bead phagosomes are shown to possess adenylyl cyclase activity, which synthesizes cAMP, and phosphodiesterase activity, which degrades cAMP. The system is regulated by protein kinase A (PKA). Increasing cAMP levels inhibited, whereas decreasing cAMP levels stimulated, actin assembly in vitro and within cells. Increasing cAMP levels also inhibited phagosome-lysosome fusion and acidification in cells, whereas reducing cAMP had the opposite effect. High cAMP levels induced an increase in intraphagosomal growth in macrophages of both the non-pathogenic Mycobacterium smegmatis and the pathogenic Mycobacterium tuberculosis, whereas low cAMP levels or inhibition of PKA correlated with increased bacterial destruction. We argue that the phagosome cAMP-PKA system behaves as a molecular switch that regulates phagosome actin and maturation in macrophages.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1242/jcs.03091-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/16931599-
heal.identifier.secondaryhttp://jcs.biologists.org/content/119/17/3686.full.pdf-
heal.journalNameJ Cell Scien
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2006-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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