ArticleMolecular biology of the cell2007
Phospholipase C regulation of phosphatidylinositol 3,4,5-trisphosphate-mediated chemotaxis.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 67 citations in OpenAlex.
- PI3K Signaling at the Crossroads of Lipid Metabolism and Cancer.Advances in experimental medicine and biology · 2025Review
- Quantitative Monitoring of GPCR-Mediated Spatiotemporal IPMethods in molecular biology (Clifton, N.J.) · 2024Article
- Three-dimensional stochastic simulation of chemoattractant-mediated excitability in cells.PLoS computational biology · 2021Article
- Review
- Lipids inFrontiers in cellular and infection microbiology · 2020Review
- Revisiting Drug Development Against the Neglected Tropical Disease, Amebiasis.Frontiers in cellular and infection microbiology · 2020Review
- The origins and evolution of macropinocytosis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Review
- PIKfyve/Fab1 is required for efficient V-ATPase and hydrolase delivery to phagosomes, phagosomal killing, and restriction of Legionella infection.PLoS pathogens · 2019Article
- Phosphatidylinositol Kinases and Phosphatases inFrontiers in cellular and infection microbiology · 2019Review
- OverexpressingOncotarget · 2018Article
- Assessment of Dictyostelium discoideum Response to Acute Mechanical Stimulation.Journal of visualized experiments : JoVE · 2017Article
- Altering the threshold of an excitable signal transduction network changes cell migratory modes.Nature cell biology · 2017Article
- Homo-FRET Based Biosensors and Their Application to Multiplexed Imaging of Signalling Events in Live Cells.International journal of molecular sciences · 2015Article
- Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion.EMBO molecular medicine · 2015Article
- Evolutionarily conserved coupling of adaptive and excitable networks mediates eukaryotic chemotaxis.Nature communications · 2014Article
- Dictyostelium uses ether-linked inositol phospholipids for intracellular signalling.The EMBO journal · 2014Article
- Moving towards a paradigm: common mechanisms of chemotactic signaling in Dictyostelium and mammalian leukocytes.Cellular and molecular life sciences : CMLS · 2014Review
- Bleb-driven chemotaxis of Dictyostelium cells.The Journal of cell biology · 2014Article
- SILAC-based proteomic quantification of chemoattractant-induced cytoskeleton dynamics on a second to minute timescale.Nature communications · 2014Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Generation of a phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P(3)] gradient within the plasma membrane is important for cell polarization and chemotaxis in many eukaryotic cells. The gradient is produced by the combined activity of phosphatidylinositol 3-kinase (PI3K) to increase PI(3,4,5)P(3) on the membrane nearest the polarizing signal and PI(3,4,5)P(3) dephosphorylation by phosphatase and tensin homolog deleted on chromosome ten (PTEN) elsewhere. Common to both of these enzymes is the lipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)], which is not only the substrate of PI3K and product of PTEN but also important for membrane binding of PTEN. Consequently, regulation of phospholipase C (PLC) activity, which hydrolyzes PI(4,5)P(2), could have important consequences for PI(3,4,5)P(3) localization. We investigate the role of PLC in PI(3,4,5)P(3)-mediated chemotaxis in Dictyostelium. plc-null cells are resistant to the PI3K inhibitor LY294002 and produce little PI(3,4,5)P(3) after cAMP stimulation, as monitored by the PI(3,4,5)P(3)-specific pleckstrin homology (PH)-domain of CRAC (PH(CRAC)GFP). In contrast, PLC overexpression elevates PI(3,4,5)P(3) and impairs chemotaxis in a similar way to loss of pten. PI3K localization at the leading edge of plc-null cells is unaltered, but dissociation of PTEN from the membrane is strongly reduced in both gradient and uniform stimulation with cAMP. These results indicate that local activation of PLC can control PTEN localization and suggest a novel mechanism to regulate the internal PI(3,4,5)P(3) gradient.
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