title: ALG-2 interacting protein-X (Alix) is essential for clathrin-independent endocytosis and signaling.
abstract: The molecular mechanisms and the biological functions of clathrin independent endocytosis (CIE) remain largely elusive. Alix (ALG-2 interacting protein X), has been assigned roles in membrane deformation and fission both in endosomes and at the plasma membrane. Using Alix ko cells, we show for the first time that Alix regulates fluid phase endocytosis and internalization of cargoes entering cells via CIE, but has no apparent effect on clathrin mediated endocytosis or downstream endosomal trafficking. We show that Alix acts with endophilin-A to promote CIE of cholera toxin and to regulate cell migration. We also found that Alix is required for fast endocytosis and downstream signaling of the interleukin-2 receptor giving a first indication that CIE is necessary for activation of at least some surface receptors. In addition to characterizing a new function for Alix, our results highlight Alix ko cells as a unique tool to unravel the biological consequences of CIE.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1216, F-38042 Grenoble, France.|Université Grenoble Alpes, Institut des Neurosciences, F-38042 Grenoble, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Mercier
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1216, F-38042 Grenoble, France.|Université Grenoble Alpes, Institut des Neurosciences, F-38042 Grenoble, France.
authors.forename: Marine H
authors.initials: MH
authors.lastname: Laporte
authors.affiliation: INSERM U1209, Grenoble, F-38042, France.|Université Grenoble Alpes, Institut Albert Bonniot, F-38000 Grenoble, France.|CNRS UMR 5309, F-38000 Grenoble, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Destaing
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1216, F-38042 Grenoble, France.|Université Grenoble Alpes, Institut des Neurosciences, F-38042 Grenoble, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Blot
authors.affiliation: Institut Curie, PSL Research University, Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Paris, France.|INSERM, U1143, Paris, France.|CNRS, UMR 3666, Paris, France.
authors.forename: Cédric M
authors.initials: CM
authors.lastname: Blouin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1216, F-38042 Grenoble, France.|Université Grenoble Alpes, Institut des Neurosciences, F-38042 Grenoble, France.
authors.forename: Karin
authors.initials: K
authors.lastname: Pernet-Gallay
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1216, F-38042 Grenoble, France.|Université Grenoble Alpes, Institut des Neurosciences, F-38042 Grenoble, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Chatellard
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1216, F-38042 Grenoble, France.|Université Grenoble Alpes, Institut des Neurosciences, F-38042 Grenoble, France.
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Saoudi
authors.affiliation: INSERM U1209, Grenoble, F-38042, France.|Université Grenoble Alpes, Institut Albert Bonniot, F-38000 Grenoble, France.|CNRS UMR 5309, F-38000 Grenoble, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Albiges-Rizo
authors.affiliation: Institut Curie, PSL Research University, Membrane Dynamics and Mechanics of Intracellular Signaling Laboratory, Paris, France.|INSERM, U1143, Paris, France.|CNRS, UMR 3666, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Lamaze
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1216, F-38042 Grenoble, France.|Université Grenoble Alpes, Institut des Neurosciences, F-38042 Grenoble, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Fraboulet
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1216, F-38042 Grenoble, France.|Université Grenoble Alpes, Institut des Neurosciences, F-38042 Grenoble, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Petiot
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1216, F-38042 Grenoble, France.|Université Grenoble Alpes, Institut des Neurosciences, F-38042 Grenoble, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Sadoul
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002772:Cholera Toxin / Q000378:metabolism / Q000633:toxicity; D002966:Clathrin / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D004705:Endocytosis / Q000235:genetics*; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D061251:Primary Cell Culture; D011485:Protein Binding; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D002966:Clathrin; D056827:Endosomal Sorting Complexes Required for Transport; C117020:PDCD6IP protein, human; C492144:Pdcd6ip protein, mouse; D015375:Receptors, Interleukin-2; D002772:Cholera Toxin; D000217:Acyltransferases; C018764:2-acylglycerophosphate acyltransferase