title: Annexin A5 stimulates autophagy and inhibits endocytosis.
abstract: Macroautophagy is a major lysosomal catabolic process activated particularly under starvation in eukaryotic cells. A new organelle, the autophagosome, engulfs cytoplasmic substrates, which are degraded after fusion with endosomes and/or lysosomes. During a shotgun proteome analysis of purified lysosomal membranes from mouse fibroblasts, a Ca(2+)-dependent phospholipid-binding protein, annexin A5, was found to increase on lysosomal membranes under starvation. This suggests a role for this protein, an abundant annexin with a still unknown intracellular function, in starvation-induced lysosomal degradation. Transient overexpression and silencing experiments showed that annexin A5 increased lysosomal protein degradation, and colocalisation experiments, based on GFP sensitivity to lysosomal acidic pH, indicated that this was mainly the result of inducing autophagosome-lysosome fusion. Annexin A5 also inhibited the endocytosis of a fluid-phase marker and cholera toxin, but not receptor-mediated endocytosis. Therefore, we propose a double and opposite role of annexin A5 in regulating the endocytic and autophagic pathways and the fusion of autophagosomes with lysosomes and endosomes.
authors.affiliation: Laboratorio de Biología Celular, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Ghita
authors.initials: G
authors.lastname: Ghislat
authors.forename: Carmen
authors.initials: C
authors.lastname: Aguado
authors.forename: Erwin
authors.initials: E
authors.lastname: Knecht
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D020013:Calcium Signaling; D002772:Cholera Toxin / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D005347:Fibroblasts; D005508:Food Deprivation; D006056:Golgi Apparatus / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008561:Membrane Fusion; D051379:Mice; D041681:NIH 3T3 Cells; D010588:Phagosomes / Q000378:metabolism; D021381:Protein Transport; D059748:Proteolysis; D040901:Proteomics
chemical_list: D017304:Annexin A5; D002772:Cholera Toxin