title: Inositol Polyphosphate-4-Phosphatase Type I Negatively Regulates Phagocytosis via Dephosphorylation of Phagosomal PtdIns(3,4)P2.
abstract: Phagocytosis is a highly conserved process whereby phagocytic cells engulf pathogens and apoptotic bodies. The present study focused on the role of inositol polyphosphate-4-phosphatase type I (Inpp4a) in phagocytosis. Raw264.7 cells that express shRNA against Inpp4a (shInpp4a cells) showed significantly increased phagocytic activity. The introduction of shRNA-resistant human Inpp4a abolished this increase. Macrophages from Inpp4a knockout mice showed similar increases in the phagocytic activity. Inpp4a was recruited to the phagosome membrane by a mechanism other than the direct interaction with Rab5. PtdIns(3,4)P2 increased on the phagosome of shInpp4a cells, while PtdIns(3)P significantly decreased. The results indicate that Inpp4a negatively regulates the phagocytic activity of macrophages as a member of the sequential dephosphorylation system that metabolizes phagosomal PtdIns(3,4,5)P3 to PtdIns(3)P.
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: Kaoru
authors.initials: K
authors.lastname: Hazeki
authors.affiliation: Department of Pathology and Immunology, Akita University School of Medicine, Akita 010-8543, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Sasaki
authors.affiliation: Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Yumio
authors.initials: Y
authors.lastname: Omori
authors.affiliation: Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Miyake
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: Takehiko
authors.initials: T
authors.lastname: Sasaki
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: D000818:Animals; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010587:Phagocytosis; D010588:Phagosomes / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology*; D010766:Phosphorylation
chemical_list: D010716:Phosphatidylinositols; D010744:Phosphoric Monoester Hydrolases; C053153:phosphatidylinositol-3,4-bisphosphate 4-phosphatase