ArticleJournal of cell science2013
Two distinct functions for PI3-kinases in macropinocytosis.
Article in Journal of cell science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 110 citations in OpenAlex.
- Loss of Copine D Leads to Ras Activation inCells · 2026Article
- Reconstitution of Ras-PI3Kγ membrane communication and feedback using light-induced signaling inputs.Nature communications · 2026Article
- Atypical PI3Ks coordinate chemotaxis, signaling dynamics, and multicellular development inbioRxiv : the preprint server for biology · 2026Article
- PI3K/PKB signaling network as a host target to enhance bacterial ingestion and clearance.Biologia futura · 2026Review
- Genome-Wide CRISPR Screen Reveals PIK3CA Inhibition Enhances Lipid Nanoparticle-Mediated siRNA Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Harnessing Natural Extracellular Vesicles to Combat Age-Related Diseases: From Aging Drivers to Therapeutic Opportunities.International journal of nanomedicine · 2026Review
- PIP5K-Ras bistability triggers plasma membrane symmetry breaking to define cellular polarity and regulate migration.bioRxiv : the preprint server for biology · 2025Article
- WNK1 mediates M-CSF-induced macropinocytosis to enforce macrophage lineage fidelity.Nature communications · 2025Article
- The IQGAP-related RasGAP IqgC regulates cell-substratum adhesion in Dictyostelium discoideum.Cellular & molecular biology letters · 2025Article
- Excitable Ras dynamics-based screens reveal RasGEFX is required for macropinocytosis and random cell migration.Nature communications · 2025Article
- Exploring the utility of a NGS multigene panel to predict BCG response in patients with non-muscle invasive bladder cancer.Oncology research · 2025Article
- CARMIL1-AA selectively inhibits macropinocytosis while sparing autophagy.Molecular biology of the cell · 2025Article
- Endothelial progenitor cell-derived conditioned medium mitigates chronic cerebral ischemic injury through macrophage migration inhibitory factor-activated AKT pathway.Stem cell research & therapy · 2024Article
- Mechanisms of extracellular vesicle uptake and implications for the design of cancer therapeutics.Journal of extracellular biology · 2024Review
- Why make it if you can take it: review on extracellular cholesterol uptake and its importance in breast and ovarian cancers.Journal of experimental & clinical cancer research : CR · 2024Review
- Leep2A and Leep2B function as a RasGAP complex to regulate macropinosome formation.The Journal of cell biology · 2024Article
- Making cups and rings: the 'stalled-wave' model for macropinocytosis.Biochemical Society transactions · 2024Review
- PTEN and the PTEN-like phosphatase CnrN have both distinct and overlapping roles in a Dictyostelium chemorepulsion pathway.Journal of cell science · 2024Article
- IqgC is a potent regulator of macropinocytosis in the presence of NF1 and its loading to macropinosomes is dependent on RasG.Open biology · 2024Article
- Formation and closure of macropinocytic cups in Dictyostelium.Current biology : CB · 2023Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Class-1 PI3-kinases are major regulators of the actin cytoskeleton, whose precise contributions to chemotaxis, phagocytosis and macropinocytosis remain unresolved. We used systematic genetic ablation to examine this question in growing Dictyostelium cells. Mass spectroscopy shows that a quintuple mutant lacking the entire genomic complement of class-1 PI3-kinases retains only 10% of wild-type PtdIns(3,4,5)P3 levels. Chemotaxis to folate and phagocytosis of bacteria proceed normally in the quintuple mutant but macropinocytosis is abolished. In this context PI3-kinases show specialized functions, only one of which is directly linked to gross PtdIns(3,4,5)P3 levels: macropinosomes originate in patches of PtdIns(3,4,5)P3, with associated F-actin-rich ruffles, both of which depend on PI3-kinase 1/2 (PI3K1/2) but not PI3K4, whereas conversion of ruffles into vesicles requires PI3K4. A biosensor derived from the Ras-binding domain of PI3K1 suggests that Ras is activated throughout vesicle formation. Binding assays show that RasG and RasS interact most strongly with PI3K1/2 and PI3K4, and single mutants of either Ras have severe macropinocytosis defects. Thus, the fundamental function of PI3-kinases in growing Dictyostelium cells is in macropinocytosis where they have two distinct functions, supported by at least two separate Ras proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.