Inhibition of Phosphatidic Acid Synthesis Alters the Structure of the Golgi Apparatus and Inhibits Secretion in Endocrine Cells

Siddhanta, Anirban; Backer, Jonathan M.; Shields, Dennis

doi:10.1074/jbc.275.16.12023

Cited by 108 publications

(122 citation statements)

References 73 publications

(81 reference statements)

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“…Several PI kinases and phosphatases are located on the ER, but the exact role that they play in secretion, if any, is not known (224,389,392). Membrane traffic between the ER and Golgi is inhibited when PtdOH production by PLD is blocked (21,322), but it is not clear if this is an effect on the ER or the Golgi.…”

Section: F Phosphoinositides On the Ermentioning

confidence: 99%

“…Golgi membranes isolated from cells overexpressing PLD 1 show elevated production of PtdIns(4,5)P 2 (294), consistent with stimulation of a PIP5KI enzyme by PA. In a series of studies, Shields and colleagues (322,323,346) have shown that PtdIns(4,5)P 2 is required to maintain Golgi structure and its production is regulated through the production of PA. Overexpression of a dominant negative PI4KII␤ disrupts the structure of the Golgi, perhaps by interfering with the ability of spectrin to bind to membranes (120), although it is not clear if this is due to the lack of a precursor for PtdIns(4,5)P 2 or to a direct effect of insufficient PtdIns(4)P. The release of secretory vesicles exporting hormones from the TGN requires PtdIns(4,5)P 2 (42,324). The nature of the vesicle coat, if any, involved in this transport step is not known.…”

Section: E Ptdins(4)p and Ptdins(45)p 2 On The Golgimentioning

confidence: 99%

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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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Section: F Phosphoinositides On the Ermentioning

confidence: 99%

Section: E Ptdins(4)p and Ptdins(45)p 2 On The Golgimentioning

confidence: 99%

Phosphoinositides in Constitutive Membrane Traffic

Roth

2004

Physiological Reviews

263

267

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“…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).…”

Section: Pld1mentioning

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.

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105

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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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“…For the preparation of PS or PA, 14 C-labeled PC was suspended in 500 l of diethylether, and then 500 l of a solution comprising 100 mM sodium acetate, pH 5.5, 100 mM CaCl 2 , and 5 M L-Ser was added. The reaction was started by the addition of 2.5 units of Actinomadura phospholipase D (Meito Sangyo, Tokyo, Japan), and 2.5 units of phospholipase D was added every 15 min.…”

Section: C-labeled Substrates-1-[1-mentioning

confidence: 99%

“…Several lines of evidence suggest that PA is also involved in vesicle-mediated transport and Golgi organization (11)(12)(13)(14). Recent elegant studies demonstrated that the conversion of lyso-PA, an inverted cone-shaped lipid, to PA, a cone-shaped lipid, induces fission of vesicles from the plasma membrane (15) or tubulation of the Golgi apparatus (16).…”

mentioning

confidence: 99%

A Novel Phospholipase A1 with Sequence Homology to a Mammalian Sec23p-interacting Protein, p125

Nakajima¹,

Sonoda²,

Mizoguchi³

et al. 2002

Journal of Biological Chemistry

107

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p125, a mammalian Sec23p-interacting protein, exhibits sequence homology with bovine testis phosphatidic acid-preferring phospholipase A 1 . In this study, we identified and characterized a new homologue of p125, KIAA0725p. KIAA0725p exhibited remarkable sequence similarity with p125 throughout the entire sequence determined but lacked an N-terminal proline-rich, Sec23p-interacting region. In vitro binding analysis showed that KIAA0725p does not bind to Sec23p. KIAA0725p possessed phospholipase A 1 activity preferentially for phosphatidic acid. We examined the effects of overexpression of KIAA0725p on the morphology of organelles. Overexpression of KIAA0725p, like that of p125, caused dispersion of the endoplasmic reticulum-Golgi intermediate compartment and Golgi apparatus. Different from the case of p125, overexpression of KIAA0725p resulted in dispersion of tethering proteins located in the Golgi region and caused aggregation of the endoplasmic reticulum. Our results indicate that KIAA0725p is a new member of the phosphatidic acid-preferring phospholipase A 1 protein family and suggest that the cellular function of KIAA0725p is different from that of p125.

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Inhibition of Phosphatidic Acid Synthesis Alters the Structure of the Golgi Apparatus and Inhibits Secretion in Endocrine Cells

Cited by 108 publications

References 73 publications

Phosphoinositides in Constitutive Membrane Traffic

Phosphoinositides in Constitutive Membrane Traffic

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

A Novel Phospholipase A1 with Sequence Homology to a Mammalian Sec23p-interacting Protein, p125

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