AP-1 and ARF1 control endosomal dynamics at sites of FcR mediated phagocytosis.
Phagocytosis, the mechanism of ingestion of large material and microorganisms, relies on actin polymerization and on the focal delivery of intracellular endocytic compartments. The molecular mechanisms involved in the formation and delivery of the endocytic vesicles that are recruited at sites of phagocytosis are not well characterized. Here we show that adaptor protein (AP)-1 but not AP-2 clathrin adaptor complexes are recruited early below the sites of particle attachment and are required for efficient receptor-mediated phagocytosis in murine macrophages. Clathrin, however, is not recruited with the AP complexes. We further show that the recruitment of AP-1-positive structures at sites of phagocytosis is regulated by the GTP-binding protein ARF1 but is not sensitive to brefeldin A. Furthermore, AP-1 depletion leads to increased surface levels of TNF-alpha, a cargo known to traffic through the endosomes to the plasma membrane upon stimulation of the macrophages. Together, our results support a clathrin-independent role for AP complexes in endosomal dynamics in macrophages by retaining some cargo proteins, a process important for membrane remodeling during phagocytosis.
Braun
Virginie
V
Institut Curie, Centre de Recherche, Paris, F-75248 France.
Deschamps
Chantal
C
Raposo
Graça
G
Benaroch
Philippe
P
Benmerah
Alexandre
A
Chavrier
Philippe
P
Niedergang
Florence
F
D020823:ADP-Ribosylation Factor 1 / Q000235:genetics / Q000378:metabolism*; D033963:Adaptor Protein Complex 3 / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism; D006801:Humans; D051379:Mice; D010587:Phagocytosis; D011485:Protein Binding; D021381:Protein Transport; D011961:Receptors, Fc / Q000378:metabolism*; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D033963:Adaptor Protein Complex 3; D015415:Biomarkers; D002966:Clathrin; D011961:Receptors, Fc; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D020823:ADP-Ribosylation Factor 1