Coordinated Ras and Rac Activity Shapes Macropinocytic Cups and Enables Phagocytosis of Geometrically Diverse Bacteria.
- Buckley CM Department of Biomedical Sciences, University of Sheffield, Sheffield S10 2TT, UK.
- Pots H Department of Cell Biochemistry, University of Groningen, Groningen 9747 AG, Netherlands.
- Gueho A Department of Biochemistry, Faculty of Sciences, Sciences II, University of Geneva, CH-1211-Geneva-4, Switzerland.
- Vines JH Department of Biomedical Sciences, University of Sheffield, Sheffield S10 2TT, UK.
- Munn CJ Department of Biomedical Sciences, University of Sheffield, Sheffield S10 2TT, UK.
- Phillips BA Department of Biomedical Sciences, University of Sheffield, Sheffield S10 2TT, UK.
- Gilsbach B German Centre for Neurodegenerative Diseases, Tübingen 72076, Germany.
- Traynor D MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
- Nikolaev A Department of Biomedical Sciences, University of Sheffield, Sheffield S10 2TT, UK.
- Soldati T Department of Biochemistry, Faculty of Sciences, Sciences II, University of Geneva, CH-1211-Geneva-4, Switzerland.
- Parnell AJ Department of Physics and Astronomy, University of Sheffield, Sheffield S3 7RH, UK.
- Kortholt A Department of Cell Biochemistry, University of Groningen, Groningen 9747 AG, Netherlands.
- King JS Department of Biomedical Sciences, University of Sheffield, Sheffield S10 2TT, UK. Electronic address: jason.king@sheffield.ac.uk.
- 2020-06-13
Published in:
- Current biology : CB. - 2020
English
Engulfment of extracellular material by phagocytosis or macropinocytosis depends on the ability of cells to generate specialized cup-shaped protrusions. To effectively capture and internalize their targets, these cups are organized into a ring or ruffle of actin-driven protrusion encircling a non-protrusive interior domain. These functional domains depend on the combined activities of multiple Ras and Rho family small GTPases, but how their activities are integrated and differentially regulated over space and time is unknown. Here, we show that the amoeba Dictyostelium discoideum coordinates Ras and Rac activity using the multidomain protein RGBARG (RCC1, RhoGEF, BAR, and RasGAP-containing protein). We find RGBARG uses a tripartite mechanism of Ras, Rac, and phospholipid interactions to localize at the protruding edge and interface with the interior of both macropinocytic and phagocytic cups. There, we propose RGBARG shapes the protrusion by expanding Rac activation at the rim while suppressing expansion of the active Ras interior domain. Consequently, cells lacking RGBARG form enlarged, flat interior domains unable to generate large macropinosomes. During phagocytosis, we find that disruption of RGBARG causes a geometry-specific defect in engulfing rod-shaped bacteria and ellipsoidal beads. This demonstrates the importance of coordinating small GTPase activities during engulfment of more complex shapes and thus the full physiological range of microbes, and how this is achieved in a model professional phagocyte.
- Language
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- English
- Open access status
- hybrid
- Identifiers
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- DOI 10.1016/j.cub.2020.05.049
- PMID 32531280
- Persistent URL
- https://sonar.ch/global/documents/230296
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