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.
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Research Article|
December 05 2014
Inpp5e increases the Rab5 association and phosphatidylinositol 3-phosphate accumulation at the phagosome through an interaction with Rab20
Tomohiro Segawa;
Tomohiro Segawa
*Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
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Kaoru Hazeki;
Kaoru Hazeki
1
*Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
1To whom correspondence should be addressed (email khazeki@hiroshima-u.ac.jp).
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Kiyomi Nigorikawa;
Kiyomi Nigorikawa
*Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
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Shin Morioka;
Shin Morioka
*Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
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Ying Guo;
Ying Guo
*Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
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Shunsuke Takasuga;
Shunsuke Takasuga
†Department of Pathology and Immunology, Akita University School of Medicine, Akita 010-8543, Japan
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Ken Asanuma;
Ken Asanuma
†Department of Pathology and Immunology, Akita University School of Medicine, Akita 010-8543, Japan
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Osamu Hazeki
Osamu Hazeki
*Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
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Publisher: Portland Press Ltd
Received:
July 18 2014
Revision Received:
September 15 2014
Accepted:
October 01 2014
Accepted Manuscript online:
October 01 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 464 (3): 365–375.
Article history
Received:
July 18 2014
Revision Received:
September 15 2014
Accepted:
October 01 2014
Accepted Manuscript online:
October 01 2014
Citation
Tomohiro Segawa, Kaoru Hazeki, Kiyomi Nigorikawa, Shin Morioka, Ying Guo, Shunsuke Takasuga, Ken Asanuma, Osamu Hazeki; Inpp5e increases the Rab5 association and phosphatidylinositol 3-phosphate accumulation at the phagosome through an interaction with Rab20. Biochem J 15 December 2014; 464 (3): 365–375. doi: https://doi.org/10.1042/BJ20140916
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