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Article |
Essential and unique roles of PIP5K-
and -
in Fc receptor-mediated phagocytosis
Correspondence to Helen L. Yin: helen.yin{at}utsouthwestern.edu
The actin cytoskeleton is dynamically remodeled during Fc
receptor (FcR)-mediated phagocytosis in a phosphatidylinositol (4,5)-bisphosphate (PIP2)-dependent manner. We investigated the role of type I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) and 
isoforms, which synthesize PIP2, during phagocytosis. PIP5K-–/– bone marrow–derived macrophages (BMM) have a highly polymerized actin cytoskeleton and are defective in attachment to IgG-opsonized particles and FcR clustering. Delivery of exogenous PIP2 rescued these defects. PIP5K- 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- by RNA interference inhibits particle attachment. In contrast, PIP5K- 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- but not PIP5K- is transiently activated by spleen tyrosine kinase–mediated phosphorylation. We propose that PIP5K- acts upstream of Rac/Rho and that the differential regulation of PIP5K- and - allows them to work in tandem to modulate the actin cytoskeleton during the attachment and ingestion phases of phagocytosis.
Abbreviations used in this paper: BMM, bone marrow–derived macrophages; C3T, C3 transferase; DIC, differential interference contrast; DN, dominant negative; ERK, extracellular signal-regulated kinase; Fc
R, Fc receptor; HPLC, high-pressure liquid chromatography; IC, immune complexes; Jasp, jasplakinolide; Latr B, latrunculin B; PIP2, phosphatidylinositol (4,5)-bisphosphate; PIP5K, type I phosphatidylinositol 4-phosphate 5-kinase; PV, pervanadate; Syk, spleen tyrosine kinase; TLC, thin layer chromatography; WASP, Wiskott-Aldrich syndrome protein; WT, wild type.
© 2009 Mao et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
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