Cloning and subcellular localization of a human phosphatidylinositol 3-phosphate 5-kinase, PIKfyve/Fab1

Cabezas, Alicia; Pattni, Krupa; Stenmark, Harald

doi:10.1016/j.gene.2005.11.009

Cited by 48 publications

(40 citation statements)

References 40 publications

(53 reference statements)

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“…PIKfyve recruitment at membranes was then measured as the number of GFP puncta in transfected cells for each condition. As previously described, control cells presented a large cytoplasmic pool of PIKfyve as well as a number of small puncta, revealing the protein association with endosomal vesicles (24,27) (Fig. 6 A and D).…”

Section: Cvpb Localizes At Ccvs and Early Endosomes Triggering Endosomesupporting

confidence: 76%

Coxiella burnetii effector CvpB modulates phosphoinositide metabolism for optimal vacuole development

Martínez

Allombert

Cantet

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

129

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The Q fever bacterium Coxiella burnetii replicates inside host cells within a large Coxiella-containing vacuole (CCV) whose biogenesis relies on the Dot/Icm-dependent secretion of bacterial effectors. Several membrane trafficking pathways contribute membranes, proteins, and lipids for CCV biogenesis. These include the endocytic and autophagy pathways, which are characterized by phosphatidylinositol 3-phosphate [PI(3)P]-positive membranes. Here we show that the C. burnetii secreted effector Coxiella vacuolar protein B (CvpB) binds PI(3)P and phosphatidylserine (PS) on CCVs and early endosomal compartments and perturbs the activity of the phosphatidylinositol 5-kinase PIKfyve to manipulate PI(3)P metabolism. CvpB association to early endosome triggers vacuolation and clustering, leading to the channeling of large PI(3)P-positive membranes to CCVs for vacuole expansion. At CCVs, CvpB binding to early endosome-and autophagy-derived PI(3)P and the concomitant inhibition of PIKfyve favor the association of the autophagosomal machinery to CCVs for optimal homotypic fusion of the Coxiella-containing compartments. The importance of manipulating PI(3)P metabolism is highlighted by mutations in cvpB resulting in a multivacuolar phenotype, rescuable by gene complementation, indicative of a defect in CCV biogenesis. Using the insect model Galleria mellonella, we demonstrate the in vivo relevance of defective CCV biogenesis by highlighting an attenuated virulence phenotype associated with cvpB mutations.Coxiella burnetii | host-pathogen interactions | phosphoinositides

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Section: Cvpb Localizes At Ccvs and Early Endosomes Triggering Endosomesupporting

confidence: 76%

Coxiella burnetii effector CvpB modulates phosphoinositide metabolism for optimal vacuole development

Martínez

Allombert

Cantet

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

129

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“…These experiments identified a phosphoinositide kinase, PIKfyve, as a member of the cytoplasmic EGFR immune complex in five independent trials. PIKfyve synthesizes phosphatidylinositol 3,5-bisphosphate (35,36) and has been linked to endosomal dynamics and intracellular trafficking (35,(37)(38)(39)(40)(41), suggesting the hypothesis that PIKfyve is a direct mediator of EGFR transit to nuclei.…”

Section: Resultsmentioning

confidence: 99%

The Phosphoinositide Kinase PIKfyve Mediates Epidermal Growth Factor Receptor Trafficking to the Nucleus

et al. 2007

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ErbB receptor tyrosine kinases can transit to nuclei in tumor cells, where they have been shown to regulate gene expression as components of transcriptional complexes. Quantitative analysis of a human bladder cancer tissue microarray identified nuclear epidermal growth factor receptor (EGFR) in tumor cells and also showed an increased frequency of this histologic feature in cancer relative to normal tissues. This observation suggests a potential role for nuclear EGFR in bladder cancer. We confirmed that EGFR could be induced to transit to nuclei in cultured human bladder cancer cells in response to the urothelial cell growth factor and EGFR ligand heparin-binding EGF-like growth factor (HB-EGF). Mass spectrometric analysis of EGFR immune complexes from a transitional carcinoma cell line (TCCSUP) identified the phosphoinositide kinase, PIKfyve, as a potential component of the EGFR trafficking mechanism. RNA silencing indicated that PIKfyve is a mediator of HB-EGF-stimulated EGFR nuclear trafficking, EGFR binding to the cyclin D1 promoter, and cell cycle progression. These results identify a novel mediator of the EGFR transcription function and further suggest that nuclear EGFR and the lipid kinase PIKfyve may play a role in bladder oncogenesis.

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“…Furthermore, PI(3,5)P 2 localization is additionally complicated by the fact that it is a very minor lipid in nonstimulated cells, although its synthesis can be induced by osmotic stress (Cooke et al 1998). The kinase PIKfyve/Fab1p, which synthesizes PI(3,5)P 2 , contains a PI(3)Pbinding FYVE domain that presumably recruits the protein to early endosomes (Cabezas et al 2006;Ikonomov et al 2006;Rutherford et al 2006), in which the substrate PI(3)P is also found. It is thus likely that PI(3,5)P 2 synthesis begins in early endosomes, and may continue at later stages of the pathway.…”

Section: Restricted Lipid Localization Via Spatially and Temporally Cmentioning

confidence: 99%

“…Many proteins involved in the regulation of endosomal dynamics contain phospholipid-bind- Simonsen et al 1998;McBride et al 1999;Pankiv et al 2010;c Carlton et al 2004;Bonifacino and Hurley 2008;d Pons et al 2008;Harterink et al 2011;Chen et al 2013;e Lloyd et al 2002;Bache et al 2003;Pons et al 2008; f Simonsen et al 2004;Filimonenko et al 2010; g Sbrissa et al 2002a;h Cabezas et al 2006;Ikonomov et al 2006;Rutherford et al 2006; see Tooze and Elazar 2013; and references in Mayinger 2012; j Ramel et al 2011;Zolov et al 2012;Oppelt et al 2013;k Gagescu et al 2000;Leventis and Grinstein 2010;Fairn et al 2011;l Uchida et al 2011;m Mobius et al 2003;Ikonen 2008;Maxfield and van Meer 2010;n Vanier and Millat 2003;Ohgami et al 2004;Xu et al 2007;Kwon et al 2009; o Kobayashi et al 1999Kobayashi et al , 2002p Matsuo et al 2004;Kirkegaard et al 2010;Bissig et al 2013. ing domains (Fig. 3B).…”

Section: Lipids As Organizing Principles Of Peripheral Membrane Proteinsmentioning

confidence: 99%

Lipid Sorting and Multivesicular Endosome Biogenesis

Bissig

Grüenberg

2013

Cold Spring Harbor Perspectives in Biology

131

107

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Intracellular organelles, including endosomes, show differences not only in protein but also in lipid composition. It is becoming clear from the work of many laboratories that the mechanisms necessary to achieve such lipid segregation can operate at very different levels, including the membrane biophysical properties, the interactions with other lipids and proteins, and the turnover rates or distribution of metabolic enzymes. In turn, lipids can directly influence the organelle membrane properties by changing biophysical parameters and by recruiting partner effector proteins involved in protein sorting and membrane dynamics. In this review, we will discuss how lipids are sorted in endosomal membranes and how they impact on endosome functions.

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Cloning and subcellular localization of a human phosphatidylinositol 3-phosphate 5-kinase, PIKfyve/Fab1

Cited by 48 publications

References 40 publications

Coxiella burnetii effector CvpB modulates phosphoinositide metabolism for optimal vacuole development

Coxiella burnetii effector CvpB modulates phosphoinositide metabolism for optimal vacuole development

The Phosphoinositide Kinase PIKfyve Mediates Epidermal Growth Factor Receptor Trafficking to the Nucleus

Lipid Sorting and Multivesicular Endosome Biogenesis

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