Function of small GTPases in Dictyostelium macropinocytosis

TD Williams, Peggy I. Paschke, Robert R. Kay (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)
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Abstract

Macropinocytosis—the large-scale, non-specific uptake of fluid by cells—is used by Dictyostelium discoideum amoebae to obtain nutrients. These cells form circular ruffles around regions of membrane defined by a patch of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) and the activated forms of the small G-proteins Ras and Rac. When this ruffle closes, a vesicle of the medium is delivered to the cell interior for further processing. It is accepted that PIP3 is required for efficient macropinocytosis. Here, we assess the roles of Ras and Rac in Dictyostelium macropinocytosis. Gain-of-function experiments show that macropinocytosis is stimulated by persistent Ras activation and genetic analysis suggests that RasG and RasS are the key Ras proteins involved. Among the activating guanine exchange factors (GEFs), GefF is implicated in macropinocytosis by an insertional mutant. The individual roles of Rho family proteins are little understood but activation of at least some may be independent of PIP3.
Original languageEnglish
Article number20180150
Number of pages11
JournalPhilosophical transactions of the Royal Society of London. Series B, Biological sciences
Volume374
Issue number1765
Early online date17 Dec 2018
DOIs
Publication statusPublished - 4 Feb 2019

Keywords

  • Dictyostelium discoideum
  • endocytosis
  • small G-protein
  • Ras
  • Macropinocytosis
  • Rac

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