Essential and unique roles of PIP5K-gamma and -alpha in Fcgamma receptor-mediated phagocytosis.

Yuntao S. Mao, Masaki Yamaga, Xiaohui Zhu, Yongjie Wei, Hui Qiao Sun, Jing Wang, Mia Yun, Yanfeng Wang, Gilbert Di Paolo, Michael Bennett, Ira Mellman, Charles S. Abrams, Pietro De Camilli, Christopher Y. Lu, Helen L. Yin

Research output: Contribution to journalArticle

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Abstract

The actin cytoskeleton is dynamically remodeled during Fcgamma receptor (FcgammaR)-mediated phagocytosis in a phosphatidylinositol (4,5)-bisphosphate (PIP(2))-dependent manner. We investigated the role of type I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) gamma and alpha isoforms, which synthesize PIP(2), during phagocytosis. PIP5K-gamma-/- bone marrow-derived macrophages (BMM) have a highly polymerized actin cytoskeleton and are defective in attachment to IgG-opsonized particles and FcgammaR clustering. Delivery of exogenous PIP(2) rescued these defects. PIP5K-gamma knockout BMM also have more RhoA and less Rac1 activation, and pharmacological manipulations establish that they contribute to the abnormal phenotype. Likewise, depletion of PIP5K-gamma by RNA interference inhibits particle attachment. In contrast, PIP5K-alpha knockout or silencing has no effect on attachment but inhibits ingestion by decreasing Wiskott-Aldrich syndrome protein activation, and hence actin polymerization, in the nascent phagocytic cup. In addition, PIP5K-gamma but not PIP5K-alpha is transiently activated by spleen tyrosine kinase-mediated phosphorylation. We propose that PIP5K-gamma acts upstream of Rac/Rho and that the differential regulation of PIP5K-gamma and -alpha allows them to work in tandem to modulate the actin cytoskeleton during the attachment and ingestion phases of phagocytosis.

Original languageEnglish (US)
Pages (from-to)281-296
Number of pages16
JournalThe Journal of cell biology
Volume184
Issue number2
DOIs
StatePublished - Jan 26 2009

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Actin Cytoskeleton
Phagocytosis
Eating
Wiskott-Aldrich Syndrome Protein
Macrophages
phagocytosis receptor
1-phosphatidylinositol-4-phosphate 5-kinase
Phosphatidylinositols
RNA Interference
Polymerization
Cluster Analysis
Actins
Protein Isoforms
Immunoglobulin G
Phosphorylation
Pharmacology
Phenotype

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Essential and unique roles of PIP5K-gamma and -alpha in Fcgamma receptor-mediated phagocytosis. / Mao, Yuntao S.; Yamaga, Masaki; Zhu, Xiaohui; Wei, Yongjie; Sun, Hui Qiao; Wang, Jing; Yun, Mia; Wang, Yanfeng; Di Paolo, Gilbert; Bennett, Michael; Mellman, Ira; Abrams, Charles S.; De Camilli, Pietro; Lu, Christopher Y.; Yin, Helen L.

In: The Journal of cell biology, Vol. 184, No. 2, 26.01.2009, p. 281-296.

Research output: Contribution to journalArticle

Mao, YS, Yamaga, M, Zhu, X, Wei, Y, Sun, HQ, Wang, J, Yun, M, Wang, Y, Di Paolo, G, Bennett, M, Mellman, I, Abrams, CS, De Camilli, P, Lu, CY & Yin, HL 2009, 'Essential and unique roles of PIP5K-gamma and -alpha in Fcgamma receptor-mediated phagocytosis.', The Journal of cell biology, vol. 184, no. 2, pp. 281-296. https://doi.org/10.1083/jcb.200806121
Mao, Yuntao S. ; Yamaga, Masaki ; Zhu, Xiaohui ; Wei, Yongjie ; Sun, Hui Qiao ; Wang, Jing ; Yun, Mia ; Wang, Yanfeng ; Di Paolo, Gilbert ; Bennett, Michael ; Mellman, Ira ; Abrams, Charles S. ; De Camilli, Pietro ; Lu, Christopher Y. ; Yin, Helen L. / Essential and unique roles of PIP5K-gamma and -alpha in Fcgamma receptor-mediated phagocytosis. In: The Journal of cell biology. 2009 ; Vol. 184, No. 2. pp. 281-296.
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