The regulation of phospholipase D by inositol phospholipids and small GTPases

Powner, Dale; Wakelam, Michael J.O.

doi:10.1016/s0014-5793(02)03410-5

Cited by 97 publications

(73 citation statements)

References 46 publications

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“…For example, it was reported that the localization of PLD1 at presynaptic membrane zones, such as axonal neurites and growth cone-like structures, plays a crucial role in controlling the number of functional release sites and modulating neurotransmitter release (13). PLD activation also plays an important role in controlling the actin cytoskeleton and cell migration, which are crucial for regulating synaptic function (22). It is important to note that, in early Alzheimer's disease (AD), synaptic pathology is more prominent than neuronal loss (23).…”

Section: Discussionmentioning

confidence: 99%

Phospholipase D1 corrects impaired βAPP trafficking and neurite outgrowth in familial Alzheimer’s disease-linked presenilin-1 mutant neurons

Cai

Zhong²,

Wang³

et al. 2006

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

104

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T he distribution of ␤-amyloid precursor protein (␤APP) between the trans-Golgi network (TGN) and the cell surface may determine the relative generation of s␤APP␣ versus ␤-amyloid (1-5). Using a cell-free vesicle-trafficking reconstitution system derived from neuroblastoma cells, we showed previously that presenilin-1 (PS1), a major component of ␥-secretase, selectively affects ␤APP budding from the TGN and the endoplasmic reticulum (ER) (6). Familial Alzheimer's disease (FAD) PS1 mutations impair the budding of vesicles containing ␤APP, which may partially account for increased ␤APP processing via ␤-and ␥-secretases.Protein trafficking within the secretory pathway is regulated by a rigorously orchestrated sequence of events. Recruitment of cytosolic factors and coat proteins to membranes, and changes in lipid composition that promote membrane curvature and protein anchoring, are necessary for vesiculation (7,8). Estradiol-promoted ␤APP trafficking depends on the recruitment of cytosolic trafficking factor Rab11 to the TGN (3).Phospholipase D (PLD), a phospholipid-modifying enzyme, catalyzes the hydrolysis of phosphatidylcholine to generate phosphatidic acid (PA) (8-10). PLD has been shown to regulate membrane trafficking events, such as the release of secretory vesicles from the TGN (11), endocytosis (12) and exocytosis (13), and actin dynamics (14). In this study, the effects of PLD1 on ␤APP trafficking have been investigated. Of particular interest, up-regulation of PLD1 in FAD-linked PS1 mutant cells rescues impaired ␤APP trafficking from the TGN to the plasma membrane and corrects FAD-related defects in neurite outgrowth capacity. In a companion paper (15), we report that PLD1 interacts with PS1 and, through a mechanism independent of its effect on ␤APP trafficking, disrupts the ␥-secretase complex and inhibits ␥-secretase activity. Results PLD1Regulates ␤APP Trafficking. We investigated whether PLD1 might be involved in regulation of ␤APP intracellular trafficking. The effect of PLD1 on ␤APP trafficking was assessed in both PS1wt and PS1-deficient cells. Consistent with our previous observations (6), the rate of formation of ␤APP-containing vesicles from the TGN in PS1 Ϫ/Ϫ fibroblasts was increased compared with PS1wt cells (Fig. 1a). Overexpression of PLD1 in PS1wt cells increased ␤APP trafficking from the TGN to a rate comparable with that seen in PS1 Ϫ/Ϫ -deficient cells. However, PLD1 overexpression failed to increase the number of ␤APP-containing vesicles budded from the TGN in PS1 Ϫ/Ϫ fibroblasts, probably because of a maximal rate of ␤APP-containing vesicle trafficking in PS1-null cells. Inhibition of PLD1 catalytic activity by 1-butanol (an inhibitor of PLD-catalyzed formation of PA) (11, 16), resulted in decreased ␤APP trafficking from the TGN in both PS1wt and PS1 Ϫ/Ϫ cells (Fig. 1b). As a control, tertiary butanol, which does not affect PLD activity (12), caused little change in ␤APP budding from the TGN. These results demonstrate that PLD1 can affect ␤APP trafficking through a PS1-independent m...

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Section: Discussionmentioning

confidence: 99%

Phospholipase D1 corrects impaired βAPP trafficking and neurite outgrowth in familial Alzheimer’s disease-linked presenilin-1 mutant neurons

Cai

Zhong²,

Wang³

et al. 2006

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

104

View full text Add to dashboard Cite

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“…The cells were washed in PBS and scraped into PBS with 0.05% SDS, and the lipids were extracted using chloroform:methanol:aqueous (8:4:3 by volume), before separation by TLC on K6 Silica Gel 60 developed with the organic phase of 2,2,4-trimethylpentane:ethyl acetate:acetic acid: H 2 O (2:13:3:10 by volume) as previously described (15). The plates were visualized on autoradiography film using En 3 Hance spray, and appropriate samples were scraped and quantitated by liquid scintillation spectrometry (cpm phosphatidylalcohol/total phospholipids)/(cpm basal phosphatidylalcohol/basal total phospholipids).…”

Section: Methodsmentioning

confidence: 99%

Phospholipase D1 Regulates Secretagogue-stimulated Insulin Release in Pancreatic β-Cells

Hughes

Elgundi

Huang

et al. 2004

Journal of Biological Chemistry

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Phospholipase D (PLD) has been strongly implicated in the regulation of Golgi trafficking as well as endocytosis and exocytosis. Our aim was to investigate the role of PLD in regulating the biphasic exocytosis of insulin from pancreatic ␤-cells that is essential for mammalian glucose homeostasis. We observed that PLD activity in MIN6 pancreatic ␤-cells is closely coupled to secretion. Cellular PLD activity was increased in response to a variety of secretagogues including the nutrient glucose and the cholinergic receptor agonist carbamoylcholine. Conversely, pharmacological or hormonal inhibition of stimulated secretion reduced PLD activity. Most importantly, blockade of PLD-catalyzed phosphatidic acid formation using butan-1-ol inhibited insulin secretion in both MIN6 cells and isolated pancreatic islets. It was further established that PLD activity was required for both the first and the second phase of glucose-stimulated insulin release, suggesting a role in the very distal steps of exocytosis, beyond granule recruitment into a readily releasable pool. Visualization of granules using green fluorescent protein-phogrin confirmed a requirement for PLD prior to granule fusion with the plasma membrane. PLD1 was shown to be the predominant isoform in MIN6 cells, and it was located at least partially on insulin granules. Overexpression of wild-type or a dominant negative catalytically inactive mutant of PLD1 augmented or inhibited secretagogue-stimulated secretion, respectively. The results suggest that phosphatidic acid formation on the granule membrane by PLD1 is essential for the regulated secretion of insulin from pancreatic ␤-cells.

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“…Additional information on PH domains and the proteins that contain them can be obtained from recent review articles (23,200,278,303).…”

Section: A Ph Domainsmentioning

confidence: 99%

Phosphoinositides in Constitutive Membrane Traffic

Roth

2004

Physiological Reviews

263

267

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Proteins that make, consume, and bind to phosphoinositides are important for constitutive membrane traffic. Different phosphoinositides are concentrated in different parts of the central vacuolar pathway, with phosphatidylinositol 4-phosphate predominate on Golgi, phosphatidylinositol 4,5-bisphosphate predominate at the plasma membrane, phosphatidylinositol 3-phosphate the major phosphoinositide on early endosomes, and phosphatidylinositol 3,5-bisphosphate found on late endocytic organelles. This spatial segregation may be the mechanism by which the direction of membrane traffic is controlled. Phosphoinositides increase the affinity of membranes for peripheral membrane proteins that function for sorting protein cargo or for the docking and fusion of transport vesicles. This implies that constitutive membrane traffic may be regulated by the mechanisms that control the activity of the enzymes that produce and consume phosphoinositides. Although the lipid kinases and phosphatases that function in constitutive membrane traffic are beginning to be identified, their regulation is poorly understood.

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The regulation of phospholipase D by inositol phospholipids and small GTPases

Cited by 97 publications

References 46 publications

Phospholipase D1 corrects impaired βAPP trafficking and neurite outgrowth in familial Alzheimer’s disease-linked presenilin-1 mutant neurons

Phospholipase D1 corrects impaired βAPP trafficking and neurite outgrowth in familial Alzheimer’s disease-linked presenilin-1 mutant neurons

Phospholipase D1 Regulates Secretagogue-stimulated Insulin Release in Pancreatic β-Cells

Phosphoinositides in Constitutive Membrane Traffic

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