title: PtdIns4KIIα generates endosomal PtdIns(4)P and is required for receptor sorting at early endosomes.
abstract: Phosphatidylinositol 4-kinase IIα (PtdIns4KIIα) localizes to the trans-Golgi network and endosomal compartments and has been implicated in the regulation of endosomal traffic, but the roles of both its enzymatic activity and the site of its action have not been elucidated. This study shows that PtdIns4KIIα is required for production of endosomal phosphatidylinositol 4-phosphate (PtdIns(4)P) on early endosomes and for the sorting of transferrin and epidermal growth factor receptor into recycling and degradative pathways. Depletion of PtdIns4KIIα with small interfering RNA significantly reduced the amount of vesicular PtdIns(4)P on early endosomes but not on Golgi membranes. Cells depleted of PtdIns4KIIα had an impaired ability to sort molecules destined for recycling from early endosomes. We further identify the Eps15 homology domain-containing protein 3 (EHD3) as a possible endosomal effector of PtdIns4KIIα. Tubular endosomes containing EHD3 were shortened and became more vesicular in PtdIns4KIIα-depleted cells. Endosomal PtdIns(4,5)P2 was also significantly reduced in PtdIns4KIIα-depleted cells. These results show that PtdIns4KIIα regulates receptor sorting at early endosomes through a PtdIns(4)P-dependent pathway and contributes substrate for the synthesis of endosomal PtdIns(4,5)P2.
authors.affiliation: Medical Research Institute, Tokyo Women's Medical University, Tokyo 162-8666, Japan Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Henmi
authors.affiliation: Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Morikawa
authors.affiliation: Medical Research Institute, Tokyo Women's Medical University, Tokyo 162-8666, Japan Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Oe
authors.affiliation: Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Narumi
authors.initials: N
authors.lastname: Ikeda
authors.affiliation: Field of Veterinary Pathobiology, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan.
authors.forename: Akikazu
authors.initials: A
authors.lastname: Fujita
authors.affiliation: Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Takei
authors.affiliation: Lipid and Membrane Biology Group, UCL Institute for Liver and Digestive Health, Division of Medicine, University College London, London NW3 2PF, United Kingdom tanabe.kenji@twmu.ac.jp s.minogue@ucl.ac.uk.
authors.forename: Shane
authors.initials: S
authors.lastname: Minogue
authors.affiliation: Medical Research Institute, Tokyo Women's Medical University, Tokyo 162-8666, Japan Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan tanabe.kenji@twmu.ac.jp s.minogue@ucl.ac.uk.
authors.forename: Kenji
authors.initials: K
authors.lastname: Tanabe
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism*; D002352:Carrier Proteins; D011992:Endosomes / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D018129:Phosphatidylinositol Phosphates / Q000096:biosynthesis*; D010716:Phosphatidylinositols / Q000378:metabolism; D021381:Protein Transport; D015398:Signal Transduction; D014168:Transferrin / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C406447:EHD3 protein, human; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D014168:Transferrin; C037178:phosphatidylinositol 4-phosphate; D019870:1-Phosphatidylinositol 4-Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors
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