Coordinated Ras and Rac Activity Shapes Macropinocytic Cups and Enables Phagocytosis of Geometrically Diverse Bacteria.

Current Biology : CB
Catherine M BuckleyJason S. King

Abstract

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-specif...Continue Reading

Citations

Mar 9, 2021·Frontiers in Immunology·Maksim V BaranovGeert van den Bogaart
May 26, 2021·Current Biology : CB·Sivakami MylvaganamSergio Grinstein
Jun 16, 2021·The Journal of Cell Biology·Yvette W H Koh, Jennifer L Stow
Jun 28, 2021·Cells & Development·Robert R Kay
Jul 13, 2021·Frontiers in Cell and Developmental Biology·Markus RitterHubert H Kerschbaum
Jul 21, 2021·Molecular Aspects of Medicine·Nicolas MeansPriyabrata Mukherjee
Aug 5, 2020·Current Biology : CB·Robert R Kay

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Methods Mentioned

BETA
GTPase
GTPases
flow cytometry
FCS
Co-immunoprecipitation
co-immunoprecipitations
Fluorescence microscopy
PCR
size exclusion chromatography

Software Mentioned

Igor Pro
FlowJo
Volocity
RGBARG
GraFit
Airyscan
ImageJ
IqgC
Graphpad Prism
Zen black

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