Inositol Polyphosphate-4-Phosphatase Type I Negatively Regulates Phagocytosis via Dephosphorylation of Phagosomal PtdIns (3,4)P2

被引:12
作者
Nigorikawa, Kiyomi [1 ]
Hazeki, Kaoru [1 ]
Sasaki, Junko [2 ]
Omori, Yumio [1 ]
Miyake, Mikiko [1 ]
Morioka, Shin [1 ]
Guo, Ying [1 ]
Sasaki, Takehiko [2 ]
Hazeki, Osamu [1 ]
机构
[1] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Hiroshima 7348553, Japan
[2] Akita Univ, Dept Pathol & Immunol, Sch Med, Akita 0108543, Japan
来源
PLOS ONE | 2015年 / 10卷 / 11期
基金
日本学术振兴会;
关键词
MYOSIN-X; PHOSPHATIDYLINOSITOL; 3-KINASES; PHOSPHOINOSITIDE; 3-KINASE; ROLES; RAB5; PHOSPHATASES; ENDOCYTOSIS; ACTIVATION;
D O I
10.1371/journal.pone.0142091
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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)P-2 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)P-3 to PtdIns(3)P.
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页数:18
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