PI3K (phosphoinositide 3-kinase) α has been implicated in phagocytosis and fluid-phase pinocytosis in macrophages. The subtype-specific role of PI3K in these processes is poorly understood. To elucidate this issue, we made Raw 264.7 cells (a mouse leukaemic monocyte–macrophage cell line) deficient in each of the class-I PI3K catalytic subunits: p110α, p110β, p110δ and p110γ. Among these cells, only the p110α-deficient cells exhibited lower phagocytosis of opsonized and non-opsonized zymosan. The p110α-deficient cells also showed the impaired phagocytosis of IgG-opsonized erythrocytes and the impaired fluid-phase pinocytosis of dextran (molecular mass of 40 kDa). Receptor-mediated pinocytosis of DiI (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate)-labelled acetylated low-density lipoprotein and fluid-phase pinocytosis of Lucifer Yellow (molecular mass of 500 Da) were resistant to p110α depletion. None of these processes were impaired in cells lacking p110β, p110δ or p110γ, but were susceptible to a pan-PI3K inhibitor wortmannin. In cells deficient in the enzymes catalysing PtdIns(3,4,5)P3 breakdown [PTEN (phosphatase and tensin homologue deleted on chromosome 10) or SHIP-1 (Src-homology-2-domain-containing inositol phosphatase-1)], uptake of IgG-opsonized particles was enhanced. These results indicated that phagocytosis and fluid-phase pinocytosis of larger molecules are dependent on the lipid kinase activity of p110α, whereas pinocytosis via clathrin-coated and small non-coated vesicles may depend on subtypes of PI3Ks other than class I.
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Research Article|
September 14 2009
Specific role of phosphoinositide 3-kinase p110α in the regulation of phagocytosis and pinocytosis in macrophages
Namiko Tamura;
Namiko Tamura
1Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8553, Japan
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Kaoru Hazeki;
Kaoru Hazeki
1
1Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8553, Japan
1To whom correspondence should be addressed (email khazeki@hiroshima-u.ac.jp).
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Natsumi Okazaki;
Natsumi Okazaki
1Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8553, Japan
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Yukiko Kametani;
Yukiko Kametani
1Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8553, Japan
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Hiroki Murakami;
Hiroki Murakami
1Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8553, Japan
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Yuki Takaba;
Yuki Takaba
1Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8553, Japan
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Yuki Ishikawa;
Yuki Ishikawa
1Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8553, Japan
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Kiyomi Nigorikawa;
Kiyomi Nigorikawa
1Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8553, Japan
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Osamu Hazeki
Osamu Hazeki
1Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8553, Japan
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Publisher: Portland Press Ltd
Received:
May 05 2009
Revision Received:
June 25 2009
Accepted:
July 15 2009
Accepted Manuscript online:
July 15 2009
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 423 (1): 99–108.
Article history
Received:
May 05 2009
Revision Received:
June 25 2009
Accepted:
July 15 2009
Accepted Manuscript online:
July 15 2009
Connected Content
This is a correction to:
Why do phosphatidylinositol kinases have so many isoforms?
Citation
Namiko Tamura, Kaoru Hazeki, Natsumi Okazaki, Yukiko Kametani, Hiroki Murakami, Yuki Takaba, Yuki Ishikawa, Kiyomi Nigorikawa, Osamu Hazeki; Specific role of phosphoinositide 3-kinase p110α in the regulation of phagocytosis and pinocytosis in macrophages. Biochem J 1 October 2009; 423 (1): 99–108. doi: https://doi.org/10.1042/BJ20090687
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