Regulation of Macropinocytosis by Diacylglycerol Kinase [zeta]

Macropinosomes arise from the closure of plasma membrane ruffles to bring about the non-selective uptake of nutrients and solutes into cells. The morphological changes underlying ruffle formation and macropinosome biogenesis are driven by actin cytoskeleton rearrangements under the control of the Rh...

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Bibliographic Details
Published in:PloS one 2015-12, Vol.10 (12)
Main Authors: Ard, Ryan, Mulatz, Kirk, Pomoransky, Julia L, Parks, Robin J, Trinkle-Mulcahy, Laura, Bell, John C, Gee, Stephen H
Format: Article
Language:English
Subjects:
Diacylglycerol
Health aspects
Phosphotransferases
Physiological aspects
Physiological regulation
Pinocytosis
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Summary:Macropinosomes arise from the closure of plasma membrane ruffles to bring about the non-selective uptake of nutrients and solutes into cells. The morphological changes underlying ruffle formation and macropinosome biogenesis are driven by actin cytoskeleton rearrangements under the control of the Rho GTPase Rac1. We showed previously that Rac1 is activated by diacylglycerol kinase [zeta] (DGK[zeta]), which phosphorylates diacylglycerol to yield phosphatidic acid. Here, we show DGK[zeta] is required for optimal macropinocytosis induced by growth factor stimulation of mouse embryonic fibroblasts. Time-lapse imaging of live cells and quantitative analysis revealed DGK[zeta] was associated with membrane ruffles and nascent macropinosomes. Macropinocytosis was attenuated in DGK[zeta]-null cells, as determined by live imaging and vaccinia virus uptake experiments. Moreover, macropinosomes that did form in DGK[zeta]-null cells were smaller than those found in wild type cells. Rescue of this defect required DGK[zeta] catalytic activity, consistent with it also being required for Rac1 activation. A constitutively membrane bound DGK[zeta] mutant substantially increased the size of macropinosomes and potentiated the effect of a constitutively active Rac1 mutant on macropinocytosis. Collectively, our results suggest DGK[zeta] functions in concert with Rac1 to regulate macropinocytosis.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0144942