ArticleMolecular biology of the cell1999
The small Mr Ras-like GTPase Rap1 and the phospholipase C pathway act to regulate phagocytosis in Dictyostelium discoideum.
Article in Molecular biology of the cell, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 96 citations in OpenAlex.
- Loss of Copine D Leads to Ras Activation inCells · 2026Article
- Loss of Copine D Leads to Ras Activation inbioRxiv : the preprint server for biology · 2026Article
- Actin dynamics controlled by IqgC, a RasGAP at the crossroads between the IQGAP and fungal GAP1 families.FEBS open bio · 2026Review
- EhRacM differentially regulates macropinocytosis and motility in the enteric protozoan parasite Entamoeba histolytica.PLoS pathogens · 2024Article
- The Amoebal Model for Macropinocytosis.Sub-cellular biochemistry · 2022Article
- Mfsd8 Modulates Growth and the Early Stages of Multicellular Development inFrontiers in cell and developmental biology · 2022Article
- From Pinocytosis to Methuosis-Fluid Consumption as a Risk Factor for Cell Death.Frontiers in cell and developmental biology · 2021Review
- Article
- The origin and evolution of cell-intrinsic antibacterial defenses in eukaryotes.Current opinion in genetics & development · 2019Review
- Function of small GTPases in Dictyostelium macropinocytosis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Review
- IQGAP-related protein IqgC suppresses Ras signaling during large-scale endocytosis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Shear force-based genetic screen reveals negative regulators of cell adhesion and protrusive activity.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- A genomewide overexpression screen identifies genes involved in the phosphatidylinositol 3-kinase pathway in the human protozoan parasite Entamoeba histolytica.Eukaryotic cell · 2014Article
- A member of the Ras oncogene family, RAP1A, mediates antileishmanial activity of monastrol.The Journal of antimicrobial chemotherapy · 2013Article
- Abi1, a critical molecule coordinating actin cytoskeleton reorganization with PI-3 kinase and growth signaling.FEBS letters · 2012Review
- The professional phagocyte Dictyostelium discoideum as a model host for bacterial pathogens.Current drug targets · 2011Review
- Legionella pneumophila infection is enhanced in a RacH-null mutant of Dictyostelium.Communicative & integrative biology · 2011Article
- A Rap/phosphatidylinositol 3-kinase pathway controls pseudopod formation [corrected].Molecular biology of the cell · 2010Article
- Localized diacylglycerol-dependent stimulation of Ras and Rap1 during phagocytosis.The Journal of biological chemistry · 2009Article
- Regulation of Rap1 activity is required for differential adhesion, cell-type patterning and morphogenesis in Dictyostelium.Journal of cell science · 2009Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The function of the small-Mr Ras-like GTPase Rap1 remains largely unknown, but this protein has been demonstrated to regulate cortical actin-based morphologic changes in Dictyostelium and the oxidative burst in mammalian neutrophils. To test whether Rap1 regulates phagocytosis, we biochemically analyzed cell lines that conditionally and modestly overexpressed wild-type [Rap1 WT(+)], constitutively active [Rap1 G12T(+)], and dominant negative [Rap1 S17N(+)] forms of D. discoideum Rap1. The rates of phagocytosis of bacteria and latex beads were significantly higher in Rap1 WT(+) and Rap1 G12T(+) cells and were reduced in Rap1 S17N(+) cells. The addition of inhibitors of protein kinase A, protein kinase G, protein tyrosine kinase, or phosphatidylinositide 3-kinase did not affect phagocytosis rates in wild-type cells. In contrast, the addition of U73122 (a phospholipase C inhibitor), calphostin C (a protein kinase C inhibitor), and BAPTA-AM (an intracellular Ca2+ chelator) reduced phagocytosis rates by 90, 50, and 65%, respectively, suggesting both arms of the phospholipase C signaling pathways played a role in this process. Other protein kinase C-specific inhibitors, such as chelerythrine and bisindolylmaleimide I, did not reduce phagocytosis rates in control cells, suggesting calphostin C was affecting phagocytosis by interfering with a protein containing a diacylglycerol-binding domain. The addition of calphostin C did not reduce phagocytosis rates in Rap1 G12T(+) cells, suggesting that the putative diacylglycerol-binding protein acted upstream in a signaling pathway with Rap1. Surprisingly, macropinocytosis was significantly reduced in Rap1 WT(+) and Rap1 G12T(+) cells compared with control cells. Together our results suggest that Rap1 and Ca2+ may act together to coordinate important early events regulating phagocytosis.
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