title: TOM1 is a PI5P effector involved in the regulation of endosomal maturation.
abstract: Phosphoinositides represent a major class of lipids specifically involved in the organization of signaling cascades, maintenance of the identity of organelles and regulation of multiple intracellular trafficking steps. We previously reported that phosphatidylinositol 5-monophosphate (PI5P), produced by the Shigella flexneri phosphatase IpgD, is implicated in the endosomal sorting of the epidermal growth factor receptor (EGFR). Here, we show that the adaptor protein TOM1 is a new direct binding partner of PI5P. We identify the domain of TOM1 involved in this interaction and characterize the binding motif. Finally, we demonstrate that the recruitment of TOM1 by PI5P on signaling endosomes is responsible for the delay in EGFR degradation and fluid-phase bulk endocytosis. Taken together, our data strongly suggest that PI5P enrichment in signaling endosomes prevents endosomal maturation through the recruitment of TOM1, and point to a new function of PI5P in regulating discrete maturation steps in the endosomal system.
authors.affiliation: INSERM U1048, I2MC and Université Paul Sabatier, 31432 Toulouse, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Boal
authors.affiliation: INSERM U1048, I2MC and Université Paul Sabatier, 31432 Toulouse, France.
authors.forename: Rana
authors.initials: R
authors.lastname: Mansour
authors.affiliation: INSERM U1048, I2MC and Université Paul Sabatier, 31432 Toulouse, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Gayral
authors.affiliation: INSERM U1048, I2MC and Université Paul Sabatier, 31432 Toulouse, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Saland
authors.affiliation: INSERM U1048, I2MC and Université Paul Sabatier, 31432 Toulouse, France.
authors.forename: Gaëtan
authors.initials: G
authors.lastname: Chicanne
authors.affiliation: INSERM U1048, I2MC and Université Paul Sabatier, 31432 Toulouse, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Xuereb
authors.affiliation: CNRS; IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, F-31077 Toulouse, France Université de Toulouse; UPS; IPBS;, F-31077 Toulouse, France.
authors.forename: Marlène
authors.initials: M
authors.lastname: Marcellin
authors.affiliation: CNRS; IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, F-31077 Toulouse, France Université de Toulouse; UPS; IPBS;, F-31077 Toulouse, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Burlet-Schiltz
authors.affiliation: INSERM U786, Unité de Pathogénie microbienne moléculaire, Institut Pasteur, 75724 Paris Cedex 15, France.
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Sansonetti
authors.affiliation: INSERM U1048, I2MC and Université Paul Sabatier, 31432 Toulouse, France CHU de Toulouse, Laboratoire d'Hématologie, 31059 Toulouse Cedex 03, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Payrastre
authors.affiliation: INSERM U1048, I2MC and Université Paul Sabatier, 31432 Toulouse, France helene.tronchere@inserm.fr.
authors.forename: Hélène
authors.initials: H
authors.lastname: Tronchère
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D004705:Endocytosis / Q000235:genetics / Q000502:physiology; D011992:Endosomes / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005347:Fibroblasts; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D016297:Mutagenesis, Site-Directed; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D018129:Phosphatidylinositol Phosphates; D011506:Proteins; D034741:RNA, Small Interfering; C120296:TOM1 protein, human; C113567:phosphatidylinositol 5-phosphate; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; Phosphoinositides; Signaling endosome; TOM1; VHS domain