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Elife. 2016 Dec 13;5. pii: e20085. doi: 10.7554/eLife.20085.

A plasma membrane template for macropinocytic cups.

Author information

1
MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
2
Beatson Institute for Cancer Research, Glasgow, United Kingdom.
3
Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, United States.

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 in Dictyostelium are 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 PIP3 patches, 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.

KEYWORDS:

SCAR/WAVE; actin cytoskeleton; cell biology; dictyostelium; macropinocytosis

PMID:
27960076
PMCID:
PMC5154761
DOI:
10.7554/eLife.20085
[Indexed for MEDLINE]
Free PMC Article

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