title: Inpp5e increases the Rab5 association and phosphatidylinositol 3-phosphate accumulation at the phagosome through an interaction with Rab20.
abstract: Phosphoinositide 5'-phosphatases have been implicated in the regulation of phagocytosis. However, their precise roles in the phagocytic process are poorly understood. We prepared RAW264.7 macrophages deficient in Inpp5e (shInpp5e) to clarify the role of this lipid phosphatase. In the shInpp5e cells, the uptake of solid particles was increased and the rate of phagosome acidification was accelerated. As expected, levels of PtdIns(3,4,5)P3 and PtdIns(3,4)P2 were increased and decreased respectively, on the forming phagocytic cups of these cells. Unexpectedly, the most prominent consequence of the Inpp5e deficiency was the decreased accumulation of PtdIns3P and Rab5 on the phagosome. The expression of a constitutively active form of Rab5b in the shInpp5e cells rescued the PtdIns3P accumulation. Rab20 has been reported to regulate the activity of Rabex5, a guanine nucleotide exchange factor for Rab5. The association of Rab20 with the phagosome was remarkably abrogated in the shInpp5e cells. Over-expression of Rab20 increased phagosomal PtdIns3P accumulation and delayed its elimination. These results suggest that Inpp5e, through functional interactions with Rab20 on the phagosome, activates Rab5, which, in turn, increases PtdIns3P and delays phagosome acidification.
authors.affiliation: *Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Segawa
authors.affiliation: *Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Hazeki
authors.affiliation: *Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Nigorikawa
authors.affiliation: *Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Morioka
authors.affiliation: *Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.affiliation: †Department of Pathology and Immunology, Akita University School of Medicine, Akita 010-8543, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Takasuga
authors.affiliation: †Department of Pathology and Immunology, Akita University School of Medicine, Akita 010-8543, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Asanuma
authors.affiliation: *Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Hazeki
mesh_terms: D000143:Acids / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D010587:Phagocytosis / Q000235:genetics; D010588:Phagosomes / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology*; D011485:Protein Binding; D014162:Transfection; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism*; D000099182:Phosphoinositide 5-Phosphatases
chemical_list: D000143:Acids; D018129:Phosphatidylinositol Phosphates; D010744:Phosphoric Monoester Hydrolases; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins; D000099182:Phosphoinositide 5-Phosphatases; C055525:phosphatidylinositol 3-phosphate; C092933:Rab20 protein, mouse