title: A plasma membrane template for macropinocytic cups.
abstract: Macropinocytosis is a fundamental mechanism that allows cells to take up extracellular liquid into large vesicles. It critically depends on the formation of a ring of protrusive actin beneath the plasma membrane, which develops into the macropinocytic cup. We show that macropinocytic cups inDictyosteliumare organised around coincident intense patches of PIP3, active Ras and active Rac. These signalling patches are invariably associated with a ring of active SCAR/WAVE at their periphery, as are all examined structures based on PIP3patches, including phagocytic cups and basal waves. Patch formation does not depend on the enclosing F-actin ring, and patches become enlarged when the RasGAP NF1 is mutated, showing that Ras plays an instructive role. New macropinocytic cups predominantly form by splitting from existing ones. We propose that cup-shaped plasma membrane structures form from self-organizing patches of active Ras/PIP3, which recruit a ring of actin nucleators to their periphery.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.|Beatson Institute for Cancer Research, Glasgow, United Kingdom.
authors.forename: Douwe M
authors.identifier: 0000-0002-9512-3235
authors.initials: DM
authors.lastname: Veltman
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Williams
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Gareth
authors.initials: G
authors.lastname: Bloomfield
authors.affiliation: Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Bi-Chang
authors.initials: BC
authors.lastname: Chen
authors.affiliation: Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Betzig
authors.affiliation: Beatson Institute for Cancer Research, Glasgow, United Kingdom.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Insall
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Kay
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D004023:Dictyostelium / Q000502:physiology*; D010716:Phosphatidylinositols / Q000378:metabolism; D010873:Pinocytosis; D015800:Protozoan Proteins / Q000378:metabolism; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: D010716:Phosphatidylinositols; D015800:Protozoan Proteins; C491975:SCAR protein, Dictyostelium; D051300:Wiskott-Aldrich Syndrome Protein Family; D020744:rac GTP-Binding Proteins; D018631:ras Proteins
keywords: SCAR/WAVE; actin cytoskeleton; cell biology; dictyostelium; macropinocytosis