Proteomic Analysis of the Very Low Density Lipoprotein (VLDL) transport vesicles

Rahim, Afidah Abdul; Nafi-valencia, Erika; Siddiqi, Shaila; Basha, Riyaz; Runyon, Chukwuemeka C.; Siddiqi, Shadab A.

doi:10.1016/j.jprot.2012.01.026

Cited by 31 publications

(44 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The data presented in Fig. 1B reveal a significant enrichment of both apoB100 and Sar1b in the VTVs, which is consistent with previous reports characterizing VLDL-containing vesicles (8,10). We next sought to probe the presence of SVIP in VTV, ER, cytosol, and Golgi fractions using specific anti-SVIP antibodies.…”

Section: Svip Is Localized To the Hepatic Er Cytosol Golgi And Vtvsupporting

confidence: 89%

mentioning

confidence: 99%

“…We performed a detailed proteomic analysis to find proteins uniquely present in the VTV (10). The VTV proteome revealed several proteins that are not present in other ER-derived vesicles; one of these VTV-specific proteins was identified as a small VCP-interacting protein (SVIP) (10). SVIP is a small 9-kDa protein consisting of 76 amino acids that contains a myristoylation site at the N terminus and is a known adaptor protein for a multifunctional protein, VCP/p97 (25).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Silencing of Small Valosin-containing Protein-interacting Protein (SVIP) Reduces Very Low Density Lipoprotein (VLDL) Secretion from Rat Hepatocytes by Disrupting Its Endoplasmic Reticulum (ER)-to-Golgi Trafficking

Tiwari

Siddiqi

Zhelyabovska

et al. 2016

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The transport of nascent very low density lipoprotein (VLDL) particles from the endoplasmic reticulum (ER) to the Golgi determines their secretion by the liver and is mediated by a specialized ER-derived vesicle, the VLDL transport vesicle (VTV). Our previous studies have shown that the formation of ER-derived VTV requires proteins in addition to coat complex II proteins. The VTV proteome revealed that a 9-kDa protein, small valosin-containing protein-interacting protein (SVIP), is uniquely present in these specialized vesicles. Our biochemical and morphological data indicate that the VTV contains SVIP. Using confocal microscopy and co-immunoprecipitation assays, we show that SVIP co-localizes with apolipoprotein B-100 (apoB100) and specifically interacts with VLDL apoB100 and coat complex II proteins. Treatment of ER membranes with myristic acid in the presence of cytosol increases SVIP recruitment to the ER in a concentration-dependent manner. Furthermore, we show that myristic acid treatment of hepatocytes increases both VTV budding and VLDL secretion. To determine the role of SVIP in VTV formation, we either blocked the SVIP protein using specific antibodies or silenced SVIP by siRNA in hepatocytes. Our results show that both blocking and silencing of SVIP lead to significant reduction in VTV formation. Additionally, we show that silencing of SVIP reduces VLDL secretion, suggesting a physiological role of SVIP in intracellular VLDL trafficking and secretion. We conclude that SVIP acts as a novel regulator of VTV formation by interacting with its cargo and coat proteins and has significant implications in VLDL secretion by hepatocytes.Aberrant secretion of very low density lipoproteins (VLDLs) from the liver contributes to the development of dyslipidemia, which constitutes a major risk factor for various metabolic disorders. A number of environmental and genetic factors have been identified that affect VLDL secretion. Insulin resistance is one of the most studied and a common factor that increases VLDL secretion from the liver as evident by both in vitro and in vivo studies (1-3). In contrast, hepatic infection with hepatitis C virus results in reduced VLDL secretion (4 -6). Although the significance of VLDL secretion and the factors affecting this process have been very well studied by numerous groups, the molecular mechanisms that control intracellular VLDL movement along the secretory pathway are poorly understood (7-9). We have adopted a proteomic, biochemical, and molecular approach to dissect the molecular machinery that controls intracellular VLDL trafficking and its eventual secretion (8, 10 -12).Several studies have shown that VLDLs are synthesized in the endoplasmic reticulum (ER) 3 and exported to the Golgi for their maturation (13,14). The transport of nascent VLDLs from the ER to the Golgi determines the rate of their eventual secretion, and this step is mediated by a dedicated vesicular system that utilizes a unique vesicle, the VLDL transport vesicle (VTV), which buds off the hepatic ER (7-9...

show abstract

Section: Svip Is Localized To the Hepatic Er Cytosol Golgi And Vtvsupporting

confidence: 89%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Silencing of Small Valosin-containing Protein-interacting Protein (SVIP) Reduces Very Low Density Lipoprotein (VLDL) Secretion from Rat Hepatocytes by Disrupting Its Endoplasmic Reticulum (ER)-to-Golgi Trafficking

Tiwari

Siddiqi

Zhelyabovska

et al. 2016

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Indeed, hepatic endoplasmic reticulum-derived VLDL transport vesicles in rats were reported to contain apoC-I. 45 ApoC-I was, however, not found in the endoplasmic reticulum-derived prechylomicron transport vesicles, 45 which supports the presence of other sources for chylomicron apoC-I. Our data suggest that WAT, a nonlipoprotein secreting tissue, may be a major source of TRL apoC-I in the postprandial state, secreting ≈534 pmol apoC-I/g WAT per day.…”

Section: Discussionmentioning

confidence: 99%

White Adipose Tissue Apolipoprotein C-I Secretion in Relation to Delayed Plasma Clearance of Dietary Fat in Humans

Wassef

Salem

Bissonnette

et al. 2012

ATVB

View full text Add to dashboard Cite

Objective-White adipose tissue (WAT) dysfunction is characterized by delayed clearance of dietary triglyceride-rich lipoproteins (TRL). We reported that apolipoprotein (apo) C-I, a transferable apolipoprotein that inhibits lipoprotein lipase activity when bound to TRL, was produced by a human adipocyte model. Thus, we aimed to determine whether increased WAT apoC-I secretion is related to delayed dietary fat clearance in humans. Methods and Results-After the ingestion of a 13 C-triolein-labeled high-fat meal, postmenopausal obese women with highfasting WAT apoC-I secretion (median >0.81 μmol/L per g/4 hours, n=9) had delayed postprandial plasma clearance of 13 C-triglyceride and 13 C-nonesterified fatty acids over 6 hours compared with controls. WAT apoC-I secretion over 4 hours correlated with fasting total and non-high-density lipoprotein apoC-I but not with high-density lipoprotein apoC-I and was the primary predictor of 4-hour postprandial increases in TRL apoC-I. Correction for TRL apoC-I eliminated the association of WAT apoC-I with 6-hour area under the curve of plasma 13 C-triglyceride; correction for insulin sensitivity or inflammation did not. Finally, in addition to apoC-I, WAT secreted considerable amount of apoC-II, apoC-III, and apoE over 24 hours; however, only WAT apoC-I secretion was associated with 6-hour area under the curve of plasma 13 C-triglyceride. Conclusion-Increased

show abstract

“…This may be due to the minor contribution of dietary particles to total plasma concentrations (<2%) (29). Alternatively, WAT apoC-I secretion may have a greater effect on chylomicrons than on VLDL clearance because hepatic endoplasmic reticulum-derived VLDL transport vesicles, but not prechylomicrons, were reported to contain apoC-I in rats (50). This suggests that the enrichment of chylomicrons with apoC-I takes place in the plasma.…”

Section: Direct Effect Of Human Apoc-i On In Situ Lpl Activity In 3t3mentioning

confidence: 99%

WAT apoC-I secretion: role in delayed chylomicron clearance in vivo and ex vivo in WAT in obese subjects

Cyr

Wassef

Bissonnette

et al. 2016

Journal of Lipid Research

View full text Add to dashboard Cite

The cardiometabolic risk associated with reduced HDL cholesterol (HDL-C) and/or elevated LDL cholesterol (LDL-C) has been well-established, the cardiometabolic risk associated with elevated TG-rich lipoproteins (TRLs) has not. However, elevated concentrations of TRLs have received much interest lately given their association with obesity, insulin resistance, and type 2 diabetes (1, 2). Two recent meta-analyses identified hypertriglyceridemia as a predictor of cardiovascular disease (3, 4). Although controversy exists regarding the independent contribution of fasting hypertriglyceridemia because of its inverse relationship with HDL-C (3, 5), that of postprandial hypertriglyceridemia remains sturdy even after adjustment for HDL-C (5-7). Accordingly, much research has now focused on factors that regulate postprandial TRL clearance.Clearance of postprandial TRLs is highly dependent on white adipose tissue (WAT). A fundamental function of WAT in the postprandial state is the hydrolysis of the TG core of TRLs through the activity of endothelial LPL and the uptake and storage of released NEFAs (8-10). Dysfunctional WAT has reduced metabolic flexibility and is unable to switch promptly from fasting (catabolic) to postprandial (anabolic) state. This leads to delayed TRL clearance, impaired remodeling of circulating lipoproteins, and increased TRL flux to peripheral tissues; thereby increasing cardiometabolic risks (11,12). The underlying mechanisms promoting WAT dysfunction and delayed TRL clearance are not fully understood.

show abstract

Proteomic Analysis of the Very Low Density Lipoprotein (VLDL) transport vesicles

Cited by 31 publications

References 45 publications

Silencing of Small Valosin-containing Protein-interacting Protein (SVIP) Reduces Very Low Density Lipoprotein (VLDL) Secretion from Rat Hepatocytes by Disrupting Its Endoplasmic Reticulum (ER)-to-Golgi Trafficking

Silencing of Small Valosin-containing Protein-interacting Protein (SVIP) Reduces Very Low Density Lipoprotein (VLDL) Secretion from Rat Hepatocytes by Disrupting Its Endoplasmic Reticulum (ER)-to-Golgi Trafficking

White Adipose Tissue Apolipoprotein C-I Secretion in Relation to Delayed Plasma Clearance of Dietary Fat in Humans

WAT apoC-I secretion: role in delayed chylomicron clearance in vivo and ex vivo in WAT in obese subjects

Contact Info

Product

Resources

About