Defective lysosome maturation and Legionella pneumophila replication in Dictyostelium cells mutant for the Arf GAP ACAP-A - Université Claude Bernard Lyon 1 Accéder directement au contenu
Article Dans Une Revue Journal of Cell Science Année : 2014

Defective lysosome maturation and Legionella pneumophila replication in Dictyostelium cells mutant for the Arf GAP ACAP-A

Résumé

Dictyostelium discoideum ACAP-A is an Arf GTPase-activating protein (GAP) involved in cytokinesis, cell migration and actin cytoskeleton dynamics. In mammalian cells, ACAP family members regulate endocytic protein trafficking. Here, we explored the function of ACAP-A in the endocytic pathway of D. discoideum. In the absence of ACAP-A, the efficiency of fusion between post-lysosomes and the plasma membrane was reduced, resulting in the accumulation of post-lysosomes. Moreover, internalized fluid-phase markers showed extended intracellular transit times, and the transfer kinetics of phagocyted particles from lysosomes to post-lysosomes was reduced. Neutralization of lysosomal pH, one essential step in lysosome maturation, was also delayed. Whereas expression of ACAP-A-GFP in acapA(-) cells restored normal particle transport kinetics, a mutant ACAP-A protein with no GAP activity towards the small GTPase ArfA failed to complement this defect. Taken together, these data support a role for ACAP-A in maturation of lysosomes into post-lysosomes through an ArfA-dependent mechanism. In addition, we reveal that ACAP-A is required for efficient intracellular growth of Legionella pneumophila, a pathogen known to subvert the endocytic host cell machinery for replication. This further emphasizes the role of ACAP-A in the endocytic pathway.
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Dates et versions

hal-01910947 , version 1 (01-06-2021)

Identifiants

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Nathalie Baïlo, Pierre Cosson, Steve J. Charette, Valérie E. Paquet, Patricia Doublet, et al.. Defective lysosome maturation and Legionella pneumophila replication in Dictyostelium cells mutant for the Arf GAP ACAP-A. Journal of Cell Science, 2014, 127 (Pt 21), pp.4702-4713. ⟨10.1242/jcs.154559⟩. ⟨hal-01910947⟩
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