cAMP synthesis and degradation by phagosomes regulate actin assembly and fusion events: consequences for mycobacteria
Φόρτωση...
Ημερομηνία
Συγγραφείς
Kalamidas, S. A.
Kuehnel, M. P.
Peyron, P.
Rybin, V.
Rauch, S.
Kotoulas, O. B.
Houslay, M.
Hemmings, B. A.
Gutierrez, M. G.
Anes, E.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
J Cell Sci
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
We 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.
Περιγραφή
Λέξεις-κλειδιά
Actins/*metabolism, Animals, *Cell Fusion, Cyclic AMP/*metabolism, Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit, Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/metabolism, Isoquinolines/metabolism, Lysosomes/metabolism, Macrophages/cytology/metabolism/microbiology, Mice, Microspheres, Mycobacterium/cytology/*physiology, Phagosomes/*metabolism/ultrastructure, Protein Kinase Inhibitors/metabolism, Sulfonamides/metabolism
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/16931599
http://jcs.biologists.org/content/119/17/3686.full.pdf
http://jcs.biologists.org/content/119/17/3686.full.pdf
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής