Activation of phospholipase D by the small GTPase Sar1p is required to support COPII assembly and ER export

Pathre, Purnima; Shome, Kuntala; Blumental‐Perry, Anna; Bielli, Anna; Haney, Charles J.; Alber, Sean; Watkins, Simon C.; Romero, Guillermo; Aridor, Meir

doi:10.1093/emboj/cdg390

Cited by 66 publications

(67 citation statements)

References 41 publications

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“…S2-S4), leading to functional ERES assembly (Figs 5,7). The results support a model in which regulatory activities such as lipid signaling (Blumental-Perry et al, 2006;Farhan et al, 2008;Nagaya et al, 2002;Pathre et al, 2003) control the progression of a molecular cascade that directs COPII nucleation and activity at ERES (Fig. 8).…”

Section: Discussionsupporting

confidence: 82%

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A cascade of ER exit site assembly that is regulated by p125A and lipid signals

Klinkenberg

Long

Shome

et al. 2014

Journal of Cell Science

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The inner and outer layers of COPII mediate cargo sorting and vesicle biogenesis. Sec16A and p125A (officially known as SEC23IP) proteins interact with both layers to control coat activity, yet the steps directing functional assembly at ER exit sites (ERES) remain undefined. By using temperature blocks, we find that Sec16A is spatially segregated from p125A-COPII-coated ERES prior to ER exit at a step that required p125A. p125A used lipid signals to control ERES assembly. Within p125A, we defined a C-terminal DDHD domain found in phospholipases and PI transfer proteins that recognized PA and phosphatidylinositol phosphates in vitro and was targeted to PI4P-rich membranes in cells. A conserved central SAM domain promoted self-assembly and selective lipid recognition by the DDHD domain. A basic cluster and a hydrophobic interface in the DDHD and SAM domains, respectively, were required for p125A-mediated functional ERES assembly. Lipid recognition by the SAM-DDHD module was used to stabilize membrane association and regulate the spatial segregation of COPII from Sec16A, nucleating the coat at ERES for ER exit.

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Section: Discussionsupporting

confidence: 82%

“…p125A or SNX9 were depleted by immunoprecipitation from RLC. The resulting supernatants were adjusted for protein concentration, verified for similar Sec23 and HSP70 levels, and used to measure COPII recruitment to microsomes as described previously (Pathre et al, 2003).…”

Section: Coat Recruitment To Luvs or Er Microsomesmentioning

confidence: 99%

A cascade of ER exit site assembly that is regulated by p125A and lipid signals

Klinkenberg

Long

Shome

et al. 2014

Journal of Cell Science

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“…Thus, the interaction we describe here provides a potential mechanism for integrating the requirements for COPII binding, protein phosphorylation and 14-3-3 recruitment at a single intracellular location. This notion of COPII acting as a platform for the recruitment of the necessary machinery molecules to ERES is consistent with the long-lived nature of ERES (Hammond and Glick, 2000;Stephens, 2003;Stephens et al, 2000) and the fact that COPII can recruit other machinery molecules such as SNARES (Mossessova et al, 2003), phospholipases (Pathre et al, 2003) and motor protein complexes (Watson et al, 2005).…”

Section: Discussionsupporting

confidence: 75%

PCTAIRE protein kinases interact directly with the COPII complex and modulate secretory cargo transport

Palmer

Konkel

Stephens

2005

Journal of Cell Science

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The export of secretory cargo from the endoplasmic reticulum is mediated by the COPII complex. In common with other aspects of intracellular transport, this step is regulated by protein kinase signalling. Recruitment of the COPII complex to the membrane is known to require ATP and to be blocked by the protein kinase inhibitor H-89. The identity of the specific protein kinase or kinases involved remains equivocal. Here we show that the Sec23p subunit of COPII interacts with PCTAIRE protein kinases. This interaction is shown using two-hybrid screening, direct binding and immunoprecipitation. Inhibition of PCTAIRE kinase activity by expression of a kinase-dead mutant, or specific depletion of PCTAIRE using RNAi, leads to defects in early secretory pathway function including cargo transport, as well as vesicular-tubular transport carrier (VTC) and Golgi localization. These data show a role for PCTAIRE protein kinase function in membrane traffic through the early secretory pathway.

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“…PLD1 also appears to participate in anterograde transport 27 and is activated by ARF1. Overexpression of PLD1 gave rise to small but statistically significant increases in the secretion of both VLDL 1 and VLDL 2, confirming our results in a cell-free system, 12 which suggested that PLD is important for the second step of VLDL assembly.…”

Section: Discussionmentioning

confidence: 99%

Role of ADP Ribosylation Factor 1 in the Assembly and Secretion of ApoB-100–Containing Lipoproteins

Asp

Magnusson

Rutberg

et al. 2005

ATVB

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Objective-We investigated the role of ADP ribosylation factor 1 (ARF1) in the assembly of very-low-density lipoproteins (VLDLs). Methods and Results-The dominant-negative ARF1 mutant, T31N, decreased the assembly of apoB-100 VLDL 1 (Svedberg floatation units [Sf] 60 to 400) by 80%. The decrease coincided with loss of coatamer I (COPI) from the Golgi apparatus and inhibition of anterograde transport, as demonstrated by time-lapse studies of the vesicular stomatitis virus G protein. The VLDL 1 assembly was also completely inhibited at 15°C. Thus, the antegrade transport is essential for the assembly of VLDL 1. Intracellular localization of N-acetylgalactosaminyl transferase 2 indicated that the Golgi apparatus was at least partly intact when the VLDL assembly was inhibited. Transient transfection with phospholipase D 1 increased the assembly of VLDL 1 and VLDL 2 (Sf 20 to 60). Overexpression of ARF1 in stably transfected McA-RH7777 cells increased the secretion of VLDL 2 but not of VLDL 1, which was dependent on the availability of oleic acid. Secretion of VLDL 1 increased with increasing amounts of oleic acid, and VLDL 2 secretion decreased simultaneously. Conclusions-Overexpression of ARF1 increased the assembly of VLDL 2 but not of VLDL 1, whose production was dependent on both anterograde transport and the availability of fatty acids. Key Words: ADP ribosylation factor 1 Ⅲ apolipoprotein B Ⅲ coatamer 1 Ⅲ intracellular transport Ⅲ very-low-density lipoproteins A polipoprotein B (apoB)-containing very-low-density lipoproteins (VLDLs) are formed in a 2-step process. 1-3 In the first step, apoB forms a partially lipidated particle (a primordial lipoprotein or pre-VLDL) during its cotranslational translocation to the lumen of the endoplasmic reticulum (ER). This step involves the transfer of lipids to apoB catalyzed by the microsomal triglyceride transfer protein. In the absence of lipids or microsomal triglyceride transfer protein, the translocation of apoB is halted, and the protein is retracted through the translocon and degraded by proteasomes. 4 -8 The second step, in which the major amount of triglycerides is added to pre-VLDL, is less well-characterized. This step involves the formation of apoB-free lipid droplets in the smooth ER 9 that associate with apoB-containing pre-VLDL in a compartment that is separate from the rough ER. 9,10 Thus, transport and sorting processes involved in the transfer of proteins out of the rough ER may be important for the assembly of VLDL. Consistent with this possibility, the second step can be inhibited by brefeldin A 11 and is dependent on ADP ribosylation factor 1 (ARF1) and phospholipase D (PLD) activity. 12 ARF1, a member of the Ras superfamily of GTP-binding proteins, participates in the formation of coatamer I (COPI) secretory vesicles, which perform retrograde transport from the Golgi to the ER and within the Golgi stacks. 13 ARF1 and COPI are important for the anterograde transport from the ER to the Golgi apparatus 14 -16 , and ARF1 activates PLD1. [17][18][19] In...

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Activation of phospholipase D by the small GTPase Sar1p is required to support COPII assembly and ER export

Cited by 66 publications

References 41 publications

A cascade of ER exit site assembly that is regulated by p125A and lipid signals

A cascade of ER exit site assembly that is regulated by p125A and lipid signals

PCTAIRE protein kinases interact directly with the COPII complex and modulate secretory cargo transport

Role of ADP Ribosylation Factor 1 in the Assembly and Secretion of ApoB-100–Containing Lipoproteins

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