Regulation of the actin cytoskeleton by phosphatidylinositol 4-phosphate 5 kinases

2007 ◽  
Vol 455 (1) ◽  
pp. 5-18 ◽  
Author(s):  
Yuntao S. Mao ◽  
Helen L. Yin
Keyword(s):  
Actin Cytoskeleton ◽  
Phosphatidylinositol 4

scholarly journals Arabidopsisphosphatidylinositol phosphate kinase 1 binds F-actin and recruits phosphatidylinositol 4-kinase β1 to the actin cytoskeleton.

2009 ◽  
Vol 284 (23) ◽  
pp. 16060.1-16060
Author(s):  
Amanda J. Davis ◽  
Yang Ju Im ◽  
Joshua S. Dubin ◽  
Kenneth B. Tomer ◽  
Wendy F. Boss
Keyword(s):  
Actin Cytoskeleton ◽  
Phosphatidylinositol 4

scholarly journals Essential and unique roles of PIP5K-γ and -α in Fcγ receptor-mediated phagocytosis

2009 ◽  
Vol 184 (2) ◽  
pp. 281-296 ◽  
Author(s):  
Yuntao S. Mao ◽  
Masaki Yamaga ◽  
Xiaohui Zhu ◽  
Yongjie Wei ◽  
Hui-Qiao Sun ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Actin Polymerization ◽  
Type I ◽  
Dependent Manner ◽  
Fcγ Receptor ◽  
Protein Activation ◽  
Phosphatidylinositol 4 ◽  
Syndrome Protein ◽  
Pharmacological Manipulations

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.

scholarly journals The WASH complex, an endosomal Arp2/3 activator, interacts with the Hermansky–Pudlak syndrome complex BLOC-1 and its cargo phosphatidylinositol-4-kinase type IIα

2013 ◽  
Vol 24 (14) ◽  
pp. 2269-2284 ◽  
Author(s):  
P. V. Ryder ◽  
R. Vistein ◽  
A. Gokhale ◽  
M. N. Seaman ◽  
M. A. Puthenveedu ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Adaptor Protein ◽  
Coat Proteins ◽  
Lipid Kinase ◽  
Rho Family Gtpases ◽  
Vesicle Biogenesis ◽  
Hermansky Pudlak Syndrome ◽  
Rho Family ◽  
Lysosome Related Organelles ◽  
Phosphatidylinositol 4

Vesicle biogenesis machinery components such as coat proteins can interact with the actin cytoskeleton for cargo sorting into multiple pathways. It is unknown, however, whether these interactions are a general requirement for the diverse endosome traffic routes. In this study, we identify actin cytoskeleton regulators as previously unrecognized interactors of complexes associated with the Hermansky–Pudlak syndrome. Two complexes mutated in the Hermansky–Pudlak syndrome, adaptor protein complex-3 and biogenesis of lysosome-related organelles complex-1 (BLOC-1), interact with and are regulated by the lipid kinase phosphatidylinositol-4-kinase type IIα (PI4KIIα). We therefore hypothesized that PI4KIIα interacts with novel regulators of these complexes. To test this hypothesis, we immunoaffinity purified PI4KIIα from isotope-labeled cell lysates to quantitatively identify interactors. Strikingly, PI4KIIα isolation preferentially coenriched proteins that regulate the actin cytoskeleton, including guanine exchange factors for Rho family GTPases such as RhoGEF1 and several subunits of the WASH complex. We biochemically confirmed several of these PI4KIIα interactions. Of importance, BLOC-1 complex, WASH complex, RhoGEF1, or PI4KIIα depletions altered the content and/or subcellular distribution of the BLOC-1–sensitive cargoes PI4KIIα, ATP7A, and VAMP7. We conclude that the Hermansky–Pudlak syndrome complex BLOC-1 and its cargo PI4KIIα interact with regulators of the actin cytoskeleton.

scholarly journals GOLPH3 drives cell migration by promoting Golgi reorientation and directional trafficking to the leading edge

2016 ◽  
Vol 27 (24) ◽  
pp. 3828-3840 ◽  
Author(s):  
Mengke Xing ◽  
Marshall C. Peterman ◽  
Robert L. Davis ◽  
Karen Oegema ◽  
Andrew K. Shiau ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Membrane Trafficking ◽  
Leading Edge ◽  
Invasion And Metastasis ◽  
Oncogenic Driver ◽  
Phosphatidylinositol 4 ◽  
Directional Cell Migration ◽  
Insight Into

The mechanism of directional cell migration remains an important problem, with relevance to cancer invasion and metastasis. GOLPH3 is a common oncogenic driver of human cancers, and is the first oncogene that functions at the Golgi in trafficking to the plasma membrane. Overexpression of GOLPH3 is reported to drive enhanced cell migration. Here we show that the phosphatidylinositol-4-phosphate/GOLPH3/myosin 18A/F-actin pathway that is critical for Golgi–to–plasma membrane trafficking is necessary and limiting for directional cell migration. By linking the Golgi to the actin cytoskeleton, GOLPH3 promotes reorientation of the Golgi toward the leading edge. GOLPH3 also promotes reorientation of lysosomes (but not other organelles) toward the leading edge. However, lysosome function is dispensable for migration and the GOLPH3 dependence of lysosome movement is indirect, via GOLPH3’s effect on the Golgi. By driving reorientation of the Golgi to the leading edge and driving forward trafficking, particularly to the leading edge, overexpression of GOLPH3 drives trafficking to the leading edge of the cell, which is functionally important for directional cell migration. Our identification of a novel pathway for Golgi reorientation controlled by GOLPH3 provides new insight into the mechanism of directional cell migration with important implications for understanding GOLPH3’s role in cancer.

scholarly journals MSS4, a Phosphatidylinositol-4-phosphate 5-Kinase Required for Organization of the Actin Cytoskeleton inSaccharomyces cerevisiae

1998 ◽  
Vol 273 (25) ◽  
pp. 15787-15793 ◽  
Author(s):  
Sylvane Desrivières ◽  
Frank T. Cooke ◽  
Peter J. Parker ◽  
Michael N. Hall
Keyword(s):  
Actin Cytoskeleton ◽  
Phosphatidylinositol 4

scholarly journals Calmodulin controls organization of the actin cytoskeleton via regulation of phosphatidylinositol (4,5)-bisphosphate synthesis in Saccharomyces cerevisiae

2002 ◽  
Vol 366 (3) ◽  
pp. 945-951 ◽  
Author(s):  
Sylvane DESRIVIÈRES ◽  
Frank T. COOKE ◽  
Helena MORALES-JOHANSSON ◽  
Peter J. PARKER ◽  
Michael N. HALL
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Actin Cytoskeleton ◽  
Membrane Trafficking ◽  
Binding Protein ◽  
Temperature Sensitive ◽  
Cellular Processes ◽  
Wide Range ◽  
Phosphatidylinositol 4 ◽  
Calmodulin Mutant

Phosphoinositides regulate a wide range of cellular processes, including proliferation, survival, cytoskeleton remodelling and membrane trafficking, yet the mechanisms controlling the kinases, phosphatases and lipases that modulate phosphoinositide levels are poorly understood. In the present study, we describe a mechanism controlling MSS4, the sole phosphatidylinositol (4)-phosphate 5-kinase in Saccharomyces cerevisiae. Mutations in MSS4 and CMD1, encoding the small Ca2+-binding protein calmodulin, confer similar phenotypes, including loss of viability and defects in endocytosis and in organization of the actin cytoskeleton. Overexpression of MSS4 suppresses the growth and actin defects of cmd1-226, a temperature-sensitive calmodulin mutant which is defective in the organization of the actin cytoskeleton. Finally, the cmd1-226 mutant exhibits reduced levels of phosphatidylinositol (4,5)-bisphosphate. These findings suggest that calmodulin positively controls MSS4 activity and thereby the actin cytoskeleton.

scholarly journals ArabidopsisPhosphatidylinositol Phosphate Kinase 1 Binds F-actin and Recruits Phosphatidylinositol 4-Kinase β1 to the Actin Cytoskeleton

2007 ◽  
Vol 282 (19) ◽  
pp. 14121-14131 ◽  
Author(s):  
Amanda J. Davis ◽  
Yang Ju Im ◽  
Joshua S. Dubin ◽  
Kenneth B. Tomer ◽  
Wendy F. Boss
Keyword(s):  
Actin Cytoskeleton ◽  
Phosphatidylinositol 4

scholarly journals Sac1 Lipid Phosphatase and Stt4 Phosphatidylinositol 4-Kinase Regulate a Pool of Phosphatidylinositol 4-Phosphate That Functions in the Control of the Actin Cytoskeleton and Vacuole Morphology

2001 ◽  
Vol 12 (8) ◽  
pp. 2396-2411 ◽  
Author(s):  
Michelangelo Foti ◽  
Anjon Audhya ◽  
Scott D. Emr
Keyword(s):  
Actin Cytoskeleton ◽  
Temperature Sensitive ◽  
Primary Role ◽  
Cytoskeleton Organization ◽  
Phosphoinositide Phosphatase ◽  
Actin Cytoskeleton Organization ◽  
Sensitive Allele ◽  
Phosphatidylinositol 4 ◽  
Mutant Cells

Synthesis and turnover of phosphoinositides are tightly regulated processes mediated by a set of recently identified kinases and phosphatases. We analyzed the primary role of the phosphoinositide phosphatase Sac1p in Saccharomyces cerevisiae with the use of a temperature-sensitive allele of this gene. Our analysis demonstrates that inactivation of Sac1p leads to a specific increase in the cellular levels of phosphatidylinositol 4-phosphate (PtdIns(4)P), accompanied by changes in vacuole morphology and an accumulation of lipid droplets. We have found that the majority of Sac1p localizes to the endoplasmic reticulum, and this localization is crucial for the efficient turnover of PtdIns(4)P. By generating double mutant strains harboring the sac1tsallele and one of two temperature-sensitive PtdIns 4-kinase genes,stt4tsor pik1ts, we have demonstrated that the bulk of PtdIns(4)P that accumulates insac1 mutant cells is generated by the Stt4 PtdIns 4-kinase, and not Pik1p. Consistent with these findings, inactivation of Sac1p partially rescued defects associated withstt4tsbut notpik1tsmutant cells. To analyze potential overlapping functions between Sac1p and other homologous phosphoinositide phosphatases, sac1tsmutant cells lacking various other synaptojanin-like phosphatases were generated. These double and triple mutants exacerbated the accumulation of intracellular phosphoinositides and caused defects in Golgi function. Together, our results demonstrate that Sac1p primarily turns over Stt4p-generated PtdIns(4)P and that the membrane localization of Sac1p is important for its function in vivo. Regulation of this PtdIns(4)P pool appears to be crucial for the maintenance of vacuole morphology, regulation of lipid storage, Golgi function, and actin cytoskeleton organization.

scholarly journals Reorganization of Actin Cytoskeleton by the Phosphoinositide Metabolite Glycerophosphoinositol 4-Phosphate

2003 ◽  
Vol 14 (2) ◽  
pp. 503-515 ◽  
Author(s):  
Raffaella Mancini ◽  
Enza Piccolo ◽  
Stefania Mariggio' ◽  
Beatrice Maria Filippi ◽  
Cristiano Iurisci ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Fluorescent Protein ◽  
Biological Activities ◽  
Small Gtpases ◽  
Fiber Formation ◽  
Water Soluble ◽  
Biologically Active ◽  
Intact Cells ◽  
Green Fluorescent ◽  
Phosphatidylinositol 4

Glycerophosphoinositol 4-phosphate (GroPIns-4P) is a biologically active, water-soluble phospholipase A metabolite derived from phosphatidylinositol 4-phosphate, whose cellular concentrations have been reported to increase in Ras-transformed cells. It is therefore important to understand its biological activities. Herein, we have examined whether GroPIns-4P can regulate the organization of the actin cytoskeleton, because this could be a Ras-related function involved in cell motility and metastatic invasion. We find that in serum-starved Swiss 3T3 cells, exogenously added GroPIns-4P rapidly and potently induces the formation of membrane ruffles, and, later, the formation of stress fibers. These actin structures can be regulated by the small GTPases Cdc42, Rac, and Rho. To analyze the mechanism of action of GroPIns-4P, we selectively inactivated each of these GTPases. GroPIns-4P requires active Rac and Rho, but not Cdc42, for ruffle and stress fiber formation, respectively. Moreover, GroPIns-4P induces a rapid translocation of the green fluorescent protein-tagged Rac into ruffles, and increases the fraction of GTP-bound Rac, in intact cells. The activation of Rac by GroPIns-4P was near maximal and long-lasting. Interestingly, this feature seems to be critical in the induction of actin ruffles by GroPIns-4P.

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