Uses and abuses of macropinocytosis
- 14 July 2016
- journal article
- research article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 129 (14), 2697-2705
- https://doi.org/10.1242/jcs.176149
Abstract
Macropinocytosis is a means by which eukaryotic cells ingest extracellular liquid and dissolved molecules. It is widely conserved amongst cells that can take on amoeboid form and, therefore, appears to be an ancient feature that can be traced back to an early stage of evolution. Recent advances have highlighted how this endocytic process can be subverted during pathology - certain cancer cells use macropinocytosis to feed on extracellular protein, and many viruses and bacteria use it to enter host cells. Prion and prion-like proteins can also spread and propagate from cell to cell through macropinocytosis. Progress is being made towards using macropinocytosis therapeutically, either to deliver drugs to or cause cell death by inducing catastrophically rapid fluid uptake. Mechanistically, the Ras signalling pathway plays a prominent and conserved activating role in amoebae and in mammals; mutant amoebae with abnormally high Ras activity resemble tumour cells in their increased capacity for growth using nutrients ingested through macropinocytosis. This Commentary takes a functional and evolutionary perspective to highlight progress in understanding and use of macropinocytosis, which is an ancient feeding process used by single-celled phagotrophs that has now been put to varied uses by metazoan cells and is abused in disease states, including infection and cancer.Keywords
Funding Information
- Medical Research Council (MC_U105115237)
This publication has 109 references indexed in Scilit:
- Macropinocytosis of protein is an amino acid supply route in Ras-transformed cellsNature, 2013
- Myosin I Links PIP 3 Signaling to Remodeling of the Actin Cytoskeleton in ChemotaxisScience Signaling, 2012
- Prion-like propagation of mutant superoxide dismutase-1 misfolding in neuronal cellsProceedings of the National Academy of Sciences of the United States of America, 2011
- Vaccinia virus strains use distinct forms of macropinocytosis for host-cell entryProceedings of the National Academy of Sciences of the United States of America, 2010
- The molecular physiology of activity‐dependent bulk endocytosis of synaptic vesiclesJournal of Neurochemistry, 2009
- Autophagy mediates the mitotic senescence transitionGenes & Development, 2009
- Shaping cups into phagosomes and macropinosomesNature Reviews Molecular Cell Biology, 2008
- A Unique Platform for H-Ras Signaling Involving Clathrin-independent EndocytosisMolecular Biology of the Cell, 2008
- G protein–independent Ras/PI3K/F-actin circuit regulates basic cell motilityThe Journal of cell biology, 2007
- Phosphatidylinositol-3-OH kinase direct target of RasNature, 1994