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PMID: 19153220 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

The Journal of cell biology ·Vol. 184 ·No. 2 ·2009-01-26 ·Pages 281-96

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

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.

MeSH Terms
Actins/metabolism Animals Humans Macrophages/cytology,metabolism Mice Mice, Transgenic Phagocytosis Phosphorylation Phosphotransferases (Alcohol Group Acceptor)/genetics,metabolism Protein Isoforms/genetics,metabolism Receptors, IgG/genetics,metabolism
Chemicals
Actins Protein Isoforms Receptors, IgG Phosphotransferases (Alcohol Group Acceptor) 1-phosphatidylinositol-4-phosphate 5-kinase
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Mao Yuntao S
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
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
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200806121
Published
2009-01-26
Epub
2009-00-19
Pages
281-96
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2654300
Subset
IM
Grants
NIGMS NIH HHS · R01 GM 06110 · United States
NIDA NIH HHS · P30 DA018343 · United States
NHLBI NIH HHS · R01 HL 083392 · United States
NHLBI NIH HHS · P01 HL040387 · United States
NINDS NIH HHS · R01 NS 056049 · United States
NINDS NIH HHS · R01 NS056049 · United States
NIDDK NIH HHS · R01 DK 069633 · United States
NHLBI NIH HHS · P01 HL 40387 · United States
NIDDK NIH HHS · R01 DK069633 · United States
NCI NIH HHS · R01 CA 03922-24 · United States
NIGMS NIH HHS · P50 GM 21681 · United States
NHLBI NIH HHS · R01 HL083392 · United States
NIGMS NIH HHS · P50 GM021681 · United States
External Links
PubMed source DOI: 10.1083/jcb.200806121 PMC Full Text View journal details
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