Depletion of Acyl-Coenzyme A-Binding Protein Affects Sphingolipid Synthesis and Causes Vesicle Accumulation and Membrane Defects in<i>Saccharomyces cerevisiae</i>

Gaigg, Barbara; Neergaard, Thomas B. F.; Schneiter, Roger; Hansen, Janne Hedegaard; Færgeman, Nils J.; Jensen, Niels Rosendal; Andersen, Jens R.; Friis, Jørgen; Sandhoff, Roger; Schrøder, Henrik Daa; Knudsen, Jens

doi:10.1091/mbc.12.4.1147

Cited by 129 publications

(135 citation statements)

References 50 publications

Supporting

Mentioning

118

Contrasting

Order By: Relevance

“…7) is not surprising and was observed previously in both Saccharomyces cerevisiae and animal systems (Mandrup et al, 1993;Knudsen et al, 1994;Gaigg et al, 2001;Huang et al, 2005;Oikari et al, 2008). Indeed, the increase in the contribution of saturated acyl-CoAs to the total acyl-CoA pool observed in this study is similar to results reported in yeast and mice overexpressing ACBP (Mandrup et al, 1993;Huang et al, 2005).…”

Section: Discussionsupporting

confidence: 90%

Production of a Brassica napus Low-Molecular Mass Acyl-Coenzyme A-Binding Protein in Arabidopsis Alters the Acyl-Coenzyme A Pool and Acyl Composition of Oil in Seeds

et al. 2014

View full text Add to dashboard Cite

Low-molecular mass (10 kD) cytosolic acyl-coenzyme A-binding protein (ACBP) has a substantial influence over fatty acid (FA) composition in oilseeds, possibly via an effect on the partitioning of acyl groups between elongation and desaturation pathways. Previously, we demonstrated that the expression of a Brassica napus ACBP (BnACBP) complementary DNA in the developing seeds of Arabidopsis (Arabidopsis thaliana) resulted in increased levels of polyunsaturated FAs at the expense of eicosenoic acid (20:1 cisD11 ) and saturated FAs in seed oil. In this study, we investigated whether alterations in the FA composition of seed oil at maturity were correlated with changes in the acyl-coenzyme A (CoA) pool in developing seeds of transgenic Arabidopsis expressing BnACBP. Our results indicated that both the acyl-CoA pool and seed oil of transgenic Arabidopsis lines expressing cytosolic BnACBP exhibited relative increases in linoleic acid (18:2 cisD9,12 ; 17.9%-44.4% and 7%-13.2%, respectively) and decreases in 20:1 cisD11 (38.7%-60.7% and 13.8%-16.3%, respectively). However, alterations in the FA composition of the acylCoA pool did not always correlate with those seen in the seed oil. In addition, we found that targeting of BnACBP to the endoplasmic reticulum resulted in FA compositional changes that were similar to those seen in lines expressing cytosolic BnACBP, with the most prominent exception being a relative reduction in a-linolenic acid (18:3 cisD9,12,15 ) in both the acyl-CoA pool and seed oil of the former (48.4%-48.9% and 5.3%-10.4%, respectively). Overall, these data support the role of ACBP in acyl trafficking in developing seeds and validate its use as a biotechnological tool for modifying the FA composition of seed oil.

show abstract

Section: Discussionsupporting

confidence: 90%

Production of a Brassica napus Low-Molecular Mass Acyl-Coenzyme A-Binding Protein in Arabidopsis Alters the Acyl-Coenzyme A Pool and Acyl Composition of Oil in Seeds

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Here, we found that replication of WT BMV RNA3 was inhibited 25-fold (Fig. 3) by deleting ACB1, encoding an acyl-CoA-binding factor involved in membrane sphingolipid biosynthesis (43). This finding underscores the importance of membrane properties to BMV RNA replication and implies that multiple classes of membrane lipids are required for a functional RNA replication complex.…”

Section: Discussionmentioning

confidence: 54%

Systematic, genome-wide identification of host genes affecting replication of a positive-strand RNA virus

Kushner

Lindenbach²,

Grdzelishvili³

et al. 2003

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

236

250

View full text Add to dashboard Cite

Brome mosaic virus (BMV), a member of the alphavirus-like superfamily of human-, animal-, and plant-infecting (ϩ)RNA viruses, has been studied as a model for viral RNA replication, encapsidation, recombination, and other processes (3). BMV has three genomic RNAs. RNAs 1 and 2 encode the interacting, multifunctional 1a helicase-like and 2a polymerase RNA replication factors (4, 5), which form endoplasmic reticulum (ER) membrane-associated RNA replication complexes with functional similarities to the replicative cores of retrovirus and double-strand (ds)RNA virus virions (6). RNA3 encodes protein 3a that enables infection spread between cells in natural hosts. The negative-strand [(Ϫ) RNA]3 replication intermediate also serves as a template for synthesis of a subgenomic (sg) mRNA, RNA4, which encodes the viral coat protein (Fig. 1A).The yeast Saccharomyces cerevisiae has proven a valuable model for normal and disease processes in human and other cells. The unusual ability of BMV to direct its genomic RNA replication, gene expression, encapsidation, and other processes in this yeast (7,8) has allowed traditional yeast mutagenic analyses that have identified host genes involved in multiple steps of BMV RNA replication and gene expression. Such host genes encode a wide variety of functions and contribute to diverse replication steps, including supporting and regulating viral translation, selecting and recruiting viral RNAs as replication templates, activating the RNA replication complex through chaperones, and providing a lipid profile compatible with membrane-associated viral RNA replication (9-14; reviewed in refs. 2 and 15).Here, we sought to develop a more rapid, global method to systematically identify yeast host factors with effects on BMV RNA replication by using an ordered array of yeast deletion strains (16) to assay virus replication in the absence of each of Ϸ4,500 yeast factors, which is Ϸ80% of the yeast genome. We describe screening this deletion array by using a whole-cell assay based on BMV-directed Renilla luciferase (Rluc) expression by pathways dependent on viral RNA replication and viral RNAdirected sg mRNA synthesis. The assay identified nearly 100 host genes whose absence repressed or enhanced BMV-directed Rluc expression by 3-to 25-fold. The results provide a significantly expanded view of virus-host interactions and should advance understanding of virus and cell pathways. Materials and MethodsYeast. YMI04 and ded1i yeast were described (11). Strains BY4743 (WT; ref. 17) and the homozygous diploid deletion series (BY4743 strain background; ref. 16) were from Research Genetics (Huntsville, AL). Standard yeast techniques were used (18), except for 96-well transformations, which were based on a one-step procedure (19). Briefly, yeast were grown to saturation overnight at 30°C in 96-well plates (1.2 ml per well), pelleted, suspended in 100 l of transformation mix (0.18 M LiAc, pH 5.5, 36% polyethylene glycol-3350, 90 mM DTT, 0.5 mg͞ml sheared salmon sperm DNA, and 20 g͞ml of each plasmid), incubate...

show abstract

“…Targeted disruption of the yeast ACBP gene (ACB1) revealed that ACBP deficiency results in increased levels of C18:0 acyl-CoA esters and a decrease in the amount of total C26:0 fatty acids, indicating that transport of FA toward elongation is impaired by lack of ACBP. Furthermore, sphingolipid and ceramide amounts were reduced, membrane structure was altered, and vesicular transport was compromised (23)(24)(25).…”

mentioning

confidence: 99%

Disruption of the Acyl-CoA-binding Protein Gene Delays Hepatic Adaptation to Metabolic Changes at Weaning

Neess¹,

Bloksgaard²,

Bek³

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

The mouse acyl-CoA-binding protein (ACBP) 5 /diazepam binding inhibitor is a 10-kDa intracellular protein consisting of 86 amino acids. It is highly conserved throughout evolution and expressed in all cell types in the eukaryotes investigated (1, 2). This, together with the characteristics of the ACBP promoter (3, 4), implies a housekeeping function of the gene. However, expression levels vary markedly between tissues (5) and in response to different metabolic stimuli (6 -9), thereby indicating that ACBP might perform more specialized functions in some cell types. The ACBP protein binds C 14 -C 22 acyl-CoA esters with high affinity and specificity (10, 11) and has very little or no affinity toward other ligands (11-13). From in vitro studies, ACBP is known to protect acyl-CoA esters from hydrolysis (14 -16) and to relieve acyl-CoA inhibition of a number of enzymes, including long chain acyl-CoA synthetase, acetyl-CoA carboxylase (ACC), adenine nucleotide translocase, fatty acid synthetase (FAS), carnitine palmitoyltransferase, and acyl-CoA:cholesterol acyltransferase (9, 16 -18). In addition, ACBP is known to donate acyl-CoA esters to phospholipid, glycerolipid, and cholesteryl ester (CE) synthesis (14, 18 -21). Finally, proteolytic products of secreted ACBP have been shown to have signaling functions in Dictyostelium as well as mammalian cells (22). Targeted disruption of the yeast ACBP gene (ACB1) revealed that ACBP deficiency results in increased levels of C18:0 acyl-CoA esters and a decrease in the amount of total C26:0 fatty acids, indicating that transport of FA toward elongation is impaired by lack of ACBP. Furthermore, sphingolipid and ceramide amounts were reduced, membrane structure was altered, and vesicular transport was compromised (23-25).The functions of ACBP in lipid metabolism have been further studied in different mammalian cell culture systems and animal models by both knockdown strategies and overexpression of the protein. It has been reported that knockdown of ACBP by small interfering RNA causes growth arrest and lethality in three different mammalian cell lines (26); however, data from our laboratory show that ACBP can be knocked down in many different cell systems without affecting growth and survival (27). 6 Recently, knockdown of ACBP in HepG2 cells was shown to suppress the expression of a number of genes involved in lipid biosynthesis and lead to decreased levels of saturated and monounsaturated fatty acids (28). In 3T3-L1 preadipocytes, knockdown of ACBP caused a mild impairment of adipocyte differentiation and accumulation of triacylglycerol (TAG) (27), whereas overexpression of ACBP in McA-RH7777 rat hepatoma cells resulted in increased intracellular TAG accumulation (29). Overexpression of ACBP in transgenic mice resulted in accumulation of different lipid classes, including TAG in the liver (30). These results suggest *

show abstract

Depletion of Acyl-Coenzyme A-Binding Protein Affects Sphingolipid Synthesis and Causes Vesicle Accumulation and Membrane Defects inSaccharomyces cerevisiae

Cited by 129 publications

References 50 publications

Production of a Brassica napus Low-Molecular Mass Acyl-Coenzyme A-Binding Protein in Arabidopsis Alters the Acyl-Coenzyme A Pool and Acyl Composition of Oil in Seeds

Production of a Brassica napus Low-Molecular Mass Acyl-Coenzyme A-Binding Protein in Arabidopsis Alters the Acyl-Coenzyme A Pool and Acyl Composition of Oil in Seeds

Systematic, genome-wide identification of host genes affecting replication of a positive-strand RNA virus

Disruption of the Acyl-CoA-binding Protein Gene Delays Hepatic Adaptation to Metabolic Changes at Weaning

Contact Info

Product

Resources

About