PIP3-dependent macropinocytosis is incompatible with chemotaxis

Veltman, Douwe M.; Lemieux, Michael G.; Knecht, David A.; Insall, Robert H.

doi:10.1083/jcb.201309081

Cited by 87 publications

(112 citation statements)

References 30 publications

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“…It is possible that the slow recovery of sGC/pla 2 /pia − is due to increased basal activity of these cells because they appeared to have more macropinosomes than other double-or triple-null cells. Consistently, inhibition of the PI3K pathway, which has been previously shown to be important for macropinosome formation (12), appeared to slightly improve the profile of the response in these cells.…”

Section: Role Of the Signal Transduction Network In The Response To Asupporting

confidence: 74%

“…4C, Movie S10, and Table S1). As mentioned above, the absence of PI3K activity slightly improved cell directionality likely due to the reduction in macropinosome formation (12). Overall, this finding suggests that acute mechanical stimulation might be acting on the same network that controls random activity and migration.…”

Section: Role Of the Signal Transduction Network In The Response To Asupporting

confidence: 58%

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Chemical and mechanical stimuli act on common signal transduction and cytoskeletal networks

Artemenko

Axiotakis

Borleis

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Signal transduction pathways activated by chemoattractants have been extensively studied, but little is known about the events mediating responses to mechanical stimuli. We discovered that acute mechanical perturbation of cells triggered transient activation of all tested components of the chemotactic signal transduction network, as well as actin polymerization. Similarly to chemoattractants, the shear flow-induced signal transduction events displayed features of excitability, including the ability to mount a full response irrespective of the length of the stimulation and a refractory period that is shared with that generated by chemoattractants. Loss of G protein subunits, inhibition of multiple signal transduction events, or disruption of calcium signaling attenuated the response to acute mechanical stimulation. Unlike the response to chemoattractants, an intact actin cytoskeleton was essential for reacting to mechanical perturbation. These results taken together suggest that chemotactic and mechanical stimuli trigger activation of a common signal transduction network that integrates external cues to regulate cytoskeletal activity and drive cell migration.biochemical excitability | shear stress | motility | biomechanics | inflammation

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Section: Role Of the Signal Transduction Network In The Response To Asupporting

confidence: 74%

Section: Role Of the Signal Transduction Network In The Response To Asupporting

confidence: 58%

Chemical and mechanical stimuli act on common signal transduction and cytoskeletal networks

Artemenko

Axiotakis

Borleis

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Major histocompatibility complex II (MHC-II)-dependent rearrangements of myosin II, which are required for efficient macropinocytosis at the cell anterior in dendritic cells, are incompatible with cell migration (Chabaud et al, 2015). This is similar to the situation in amoebae, where chemotaxis towards folic acid is impaired when high-frequency macropinocytosis occurs, again highlighting the broad similarities that could extend back to the common ancestors of Metazoa and amoebae (Veltman et al, 2014). As large-scale endocytosis depends on many of the same components of the actin cytoskeleton as those required for pseudopodial protrusion during cell migration, it appears that it is difficult for both processes to occur simultaneously, perhaps because different configurations of cortical actin are required in endocytic and migratory pseudopodia.…”

Section: Macropinocytosis In Immunity and Infectionmentioning

confidence: 76%

Uses and abuses of macropinocytosis

Bloomfield

Kay

2016

Journal of Cell Science

168

171

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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.

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“…Dictyostelium cells transformed with the GFP-PH CRAC expression plasmid pDM631 (74) were seeded in glass-bottomed dishes in SIH medium for 2 h before addition of yeast at fivefold excess. For time-lapse microscopy, cells were overlaid with a thin ∼1.5-mm thick sheet of 1% SIH agarose before imaging on a spinning disk microscope as above.…”

Section: V-atpasementioning

confidence: 99%

WASH drives early recycling from macropinosomes and phagosomes to maintain surface phagocytic receptors

Buckley

Gopaldass

Bosmani

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Macropinocytosis is an ancient mechanism that allows cells to harvest nutrients from extracellular media, which also allows immune cells to sample antigens from their surroundings. During macropinosome formation, bulk plasma membrane is internalized with all its integral proteins. It is vital for cells to salvage these proteins before degradation, but the mechanisms for sorting them are not known. Here we describe the evolutionarily conserved recruitment of the WASH (WASP and SCAR homolog) complex to both macropinosomes and phagosomes within a minute of internalization. Using Dictyostelium, we demonstrate that WASH drives protein sorting and recycling from macropinosomes and is thus essential to maintain surface receptor levels and sustain phagocytosis. WASH functionally interacts with the retromer complex at both early and late phases of macropinosome maturation, but mediates recycling via retromer-dependent and -independent pathways. WASH mutants consequently have decreased membrane levels of integrins and other surface proteins. This study reveals an important pathway enabling cells to sustain macropinocytosis without bulk degradation of plasma membrane components.phagocytosis | macropinocytosis | WASH | Dictyostelium | trafficking

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PIP3-dependent macropinocytosis is incompatible with chemotaxis

Abstract: In growing Dictyostelium discoideum, PIP3 is unnecessary for migration toward folate and actively inhibits chemotaxis and pseudopod formation by promoting macropinocytosis.

Cited by 87 publications

References 30 publications

Chemical and mechanical stimuli act on common signal transduction and cytoskeletal networks

Chemical and mechanical stimuli act on common signal transduction and cytoskeletal networks

Uses and abuses of macropinocytosis

WASH drives early recycling from macropinosomes and phagosomes to maintain surface phagocytic receptors

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