Essential and unique roles of PIP5K-γ and - α in Fcγ 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

75 Scopus citations

Abstract

The actin cytoskeleton is dynamically remodeled during Fcγ receptor (FcγR)-mediated phagocytosis in a phosphatidylinositol (4,5)-bisphosphate (PIP2)-dependent manner. We investigated the role of type I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) γ and α isoforms, which synthesize PIP2, during phagocytosis. PIP5K-γ-/- bone marrow - derived macrophages (BMM) have a highly polymerized actin cytoskeleton and are defective in attachment to IgG-opsonized particles and FcγR clustering. Delivery of exogenous PIP2 rescued these defects. PIP5K-γ 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-γ by RNA interference inhibits particle attachment. In contrast, PIP5K-α 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-γ but not PIP5K-α is transiently activated by spleen tyrosine kinase - mediated phosphorylation. We propose that PIP5K-γ acts upstream of Rac/Rho and that the differential regulation of PIP5K-γ and -α 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
JournalJournal of Cell Biology
Volume184
Issue number2
DOIs
StatePublished - Jan 26 2009

ASJC Scopus subject areas

  • Cell Biology

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    Mao, Y. S., Yamaga, M., Zhu, X., Wei, Y., Sun, H. Q., Wang, J., Yun, M., Wang, Y., Di Paolo, G., Bennett, M., Mellman, I., Abrams, C. S., De Camilli, P., Lu, C. Y., & Yin, H. L. (2009). Essential and unique roles of PIP5K-γ and - α in Fcγ receptor-mediated phagocytosis. Journal of Cell Biology, 184(2), 281-296. https://doi.org/10.1083/jcb.200806121