Phospholipase D Stimulates Release of Nascent Secretory Vesicles from the trans-Golgi Network
Ye-Guang Chen,Anirban Siddhanta,Cary D. Austin,Scott M. Hammond,Tsung Chang Sung,Michael A. Frohman,Andrew J. Morris,Dennis Shields +7 more
TLDR
It is demonstrated that immunoaffinity-purified human PLD1 stimulated nascent secretory vesicle budding from the TGN and ARF-1 stimulated endogenous PLD activity in Golgi membranes approximately threefold and this activation correlated with its enhancement of vesicles budding.Abstract:
Phospholipase D (PLD) is a phospholipid hydrolyzing enzyme whose activation has been implicated in mediating signal transduction pathways, cell growth, and membrane trafficking in mammalian cells. Several laboratories have demonstrated that small GTP-binding proteins including ADP-ribosylation factor (ARF) can stimulate PLD activity in vitro and an ARF-activated PLD activity has been found in Golgi membranes. Since ARF-1 has also been shown to enhance release of nascent secretory vesicles from the TGN of endocrine cells, we hypothesized that this reaction occurred via PLD activation. Using a permeabilized cell system derived from growth hormone and prolactin-secreting pituitary GH3 cells, we demonstrate that immunoaffinity-purified human PLD1 stimulated nascent secretory vesicle budding from the TGN approximately twofold. In contrast, a similarly purified but enzymatically inactive mutant form of PLD1, designated Lys898Arg, had no effect on vesicle budding when added to the permeabilized cells. The release of nascent secretory vesicles from the TGN was sensitive to 1% 1-butanol, a concentration that inhibited PLD-catalyzed formation of phosphatidic acid. Furthermore, ARF-1 stimulated endogenous PLD activity in Golgi membranes approximately threefold and this activation correlated with its enhancement of vesicle budding. Our results suggest that ARF regulation of PLD activity plays an important role in the release of nascent secretory vesicles from the TGN.read more
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References
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Journal ArticleDOI
Characterization of a GTPase-activating Protein That Stimulates GTP Hydrolysis by Both ADP-ribosylation Factor (ARF) and ARF-like Proteins COMPARISON TO THE ARD1 GAP DOMAIN
TL;DR: Purified spleen GAP accelerated hydrolysis of GTP bound to recombinant ARF1, ARF3, ARf5, and ARF6; no effect of NH2-terminal myristoylation was observed, and the ARF domain of ARD1 and Δ13ARF1 were poor substrates for ARF GAP.
Journal ArticleDOI
ARF1-regulated phospholipase D in human neutrophils is enhanced by PMA and MgATP
TL;DR: It is concluded that many of the observed effects of PMA may be dependent on the presence of the small GTP‐binding protein, ARF, and polyphosphoinositides are required for ARF1‐stimulated PLD activity.
Journal ArticleDOI
The roles of multiple pathways in regulating bombesin-stimulated phospholipase D activity in Swiss 3T3 fibroblasts.
C P Briscoe,A Martin,Michael J. Cross,Michael J. Cross,Michael J.O. Wakelam,Michael J.O. Wakelam +5 more
TL;DR: It is suggested that bombesin-stimulated phospholipase D activity is indirectly regulated by G-proteins, possibly through a kinase intermediate, and activation of protein tyrosine kinases is proposed to account for the PKC-independent arm of bombsin- Stimulated PLD activity.