Tsc13p Is Required for Fatty Acid Elongation and Localizes to a Novel Structure at the Nuclear-Vacuolar Interface in <i>Saccharomyces cerevisiae</i>

Kohlwein, Sepp D.; Eder, Sandra; Oh, Chan-Seok; Martin, Charles E.; Gable, Ken; Bačíková, Dagmar; Dunn, Teresa M.

doi:10.1128/mcb.21.1.109-125.2001

Cited by 208 publications

(257 citation statements)

References 69 publications

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“…The Ca 2ϩ -sensitive phenotype of the csg2 mutant was suppressed by several mutations that caused a reduction in the IPC-C concentrations (6). These mutations included genes involved in long chain base synthesis (lcb1, lcb2, tsc3, and tsc10) (6,9,15), palmitoyl-CoA synthesis (fas2) (9), elongation of very long chain fatty acids (tsc13) (9,16), conversion of DHS to phytosphingosine (sur2) (1), and hydroxylation of very long chain fatty acids (scs7) (1). Moreover, overproduction of Ccc2p, which may stimulate the conversion of IPC-C to IPC-D, also rescued the Ca 2ϩ -sensitive phenotype of the csg2 mutant (3).…”

Section: Discussionmentioning

confidence: 99%

Csg1p and Newly Identified Csh1p Function in Mannosylinositol Phosphorylceramide Synthesis by Interacting with Csg2p

Uemura

Kihara

Inokuchi

et al. 2003

Journal of Biological Chemistry

106

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Csg1p and Csg2p have been shown to be involved in the synthesis of mannosylinositol phosphorylceramide (MIPC) from inositol phosphorylceramide. YBR161w, termed CSH1 here, encodes a protein that exhibits a strong similarity to Csg1p. To examine whether Csh1p also functions in MIPC synthesis, we performed a [ 3 H]dihydrosphingosine labeling experiment. ⌬csg1 cells exhibited only a reduction in the synthesis of mannosylated sphingolipids compared with wild-type cells, whereas the ⌬csg1 ⌬csh1 double deletion mutant exhibited a total loss. These results indicated that Csg1p and Csh1p have redundant functions in MIPC synthesis. Analyses using ⌬csg1 and ⌬csh1 cells in the ⌬ipt1, ⌬sur2, or ⌬scs7 genetic background demonstrated that Csh1p has a different substrate specificity from Csg1p. We also revealed that Csg2p interacts with both Csg1p and Csh1p. Deletion of the CSG2 gene reduced the Csg1p activity and abolished the Csh1p activity. These results suggested that two distinct inositol phosphorylceramide mannosyltransferase complexes, Csg1p-Csg2p and Csh1p-Csg2p, exist.

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Section: Discussionmentioning

confidence: 99%

Csg1p and Newly Identified Csh1p Function in Mannosylinositol Phosphorylceramide Synthesis by Interacting with Csg2p

Uemura

Kihara

Inokuchi

et al. 2003

Journal of Biological Chemistry

106

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“…pAL2-URA was constructed for divergent constitutive expression of AtLCB1-FLAG (or AtLCB1 C144W -FLAG) and Myc-tagged AtLCB2a by replacing the GAL1 and GAL10 promoters of pESC-URA (Stratagene) with the yeast LCB2 and ADH promoters, respectively. The AtssSPTa cDNA open reading frame was inserted after the 33 HA tag in pADH1 (Kohlwein et al, 2001;Kimberlin et al, 2013).…”

Section: Yeast Growth and Expression Plasmidsmentioning

confidence: 99%

ORM Expression Alters Sphingolipid Homeostasis and Differentially Affects Ceramide Synthase Activities

et al. 2016

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Sphingolipid synthesis is tightly regulated in eukaryotes. This regulation in plants ensures sufficient sphingolipids to support growth while limiting the accumulation of sphingolipid metabolites that induce programmed cell death. Serine palmitoyltransferase (SPT) catalyzes the first step in sphingolipid biosynthesis and is considered the primary sphingolipid homeostatic regulatory point. In this report, Arabidopsis (Arabidopsis thaliana) putative SPT regulatory proteins, orosomucoidlike proteins AtORM1 and AtORM2, were found to interact physically with Arabidopsis SPT and to suppress SPT activity when coexpressed with Arabidopsis SPT subunits long-chain base1 (LCB1) and LCB2 and the small subunit of SPT in a yeast (Saccharomyces cerevisiae) SPT-deficient mutant. Consistent with a role in SPT suppression, AtORM1 and AtORM2 overexpression lines displayed increased resistance to the programmed cell death-inducing mycotoxin fumonisin B 1 , with an accompanying reduced accumulation of LCBs and C16 fatty acid-containing ceramides relative to wild-type plants. Conversely, RNA interference (RNAi) suppression lines of AtORM1 and AtORM2 displayed increased sensitivity to fumonisin B 1 and an accompanying strong increase in LCBs and C16 fatty acid-containing ceramides relative to wild-type plants. Overexpression lines also were found to have reduced activity of the class I ceramide synthase that uses C16 fatty acid acyl-coenzyme A and dihydroxy LCB substrates but increased activity of class II ceramide synthases that use very-long-chain fatty acyl-coenzyme A and trihydroxy LCB substrates. RNAi suppression lines, in contrast, displayed increased class I ceramide synthase activity but reduced class II ceramide synthase activity. These findings indicate that ORM mediation of SPT activity differentially regulates functionally distinct ceramide synthase activities as part of a broader sphingolipid homeostatic regulatory network.

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“…These stacks usually surround the nucleus and are largely devoid of nuclear pores. Finally, in ϳ5-10% of log-phase cells, the nuclear envelope at the nucleus-vacuole junction folds into teardroplike blebs that protrude into the vacuole (Kohlwein et al, 2001;Roberts et al, 2003). These blebs, which are eventually converted into intravacuolar vesicles, are involved in microautophagy of nuclear constituents, including nucleolar material, and their prevalence increases in starved cells (Roberts et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Yeast Nuclear Envelope Subdomains with Distinct Abilities to Resist Membrane Expansion

Campbell

Lorenz

Witkin

et al. 2006

MBoC

117

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Little is known about what dictates the round shape of the yeast Saccharomyces cerevisiae nucleus. In spo7⌬ mutants, the nucleus is misshapen, exhibiting a single protrusion. The Spo7 protein is part of a phosphatase complex that represses phospholipid biosynthesis. Here, we report that the nuclear protrusion of spo7⌬ mutants colocalizes with the nucleolus, whereas the nuclear compartment containing the bulk of the DNA is unaffected. Using strains in which the nucleolus is not intimately associated with the nuclear envelope, we show that the single nuclear protrusion of spo7⌬ mutants is not a result of nucleolar expansion, but rather a property of the nuclear membrane. We found that in spo7⌬ mutants the peripheral endoplasmic reticulum (ER) membrane was also expanded. Because the nuclear membrane and the ER are contiguous, this finding indicates that in spo7⌬ mutants all ER membranes, with the exception of the membrane surrounding the bulk of the DNA, undergo expansion. Our results suggest that the nuclear envelope has distinct domains that differ in their ability to resist membrane expansion in response to increased phospholipid biosynthesis. We further propose that in budding yeast there is a mechanism, or structure, that restricts nuclear membrane expansion around the bulk of the DNA. INTRODUCTIONThe nucleus has a distinct organization, characterized by the presence of internal subcompartments. Moreover, in most, but not all, cell types the nucleus adopts a round shape. Understanding how this organization and shape are achieved is of major biological and medical interest. Certain cell types, such as those found in blood lineages (e.g., neutrophils, monocytes, and eosinophils), undergo dramatic nuclear shape changes as they differentiate (Gartner et al., 1990). Cancerous states are often associated with changes in nuclear morphology, most frequently nucleolar enlargement, changes in nuclear shape, or a combination of the two (Zink et al., 2004). Although these changes provide useful diagnostic markers of cancer progression, their mechanistic basis is still poorly understood. Other diseases are also associated with changes in nuclear shape and organization. For example, Hutchinson-Gilford progeria syndrome, which leads to premature aging, is caused by a specific mutation in the gene encoding A-type lamins and is associated with nuclear shape changes . Interestingly, progeria-like changes in nuclear shape are part of the normal aging process of nonneuronal cells in Caenorhabditis elegans (Haithcock et al., 2005). Genetic defects in the nuclear lamina are also associated with several types of muscular dystrophy . Nuclear lamins and their associated proteins provide both a rigid structure that helps shape the nuclear membrane and a platform onto which protein complexes and chromatin can bind (Holaska et al., 2002). Although much has been learned in recent years about the function of nuclear lamins, many significant questions remain. For example, it is not known how diseaseassociated changes in nuclear shape affect...

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Tsc13p Is Required for Fatty Acid Elongation and Localizes to a Novel Structure at the Nuclear-Vacuolar Interface in Saccharomyces cerevisiae

Cited by 208 publications

References 69 publications

Csg1p and Newly Identified Csh1p Function in Mannosylinositol Phosphorylceramide Synthesis by Interacting with Csg2p

Csg1p and Newly Identified Csh1p Function in Mannosylinositol Phosphorylceramide Synthesis by Interacting with Csg2p

ORM Expression Alters Sphingolipid Homeostasis and Differentially Affects Ceramide Synthase Activities

Yeast Nuclear Envelope Subdomains with Distinct Abilities to Resist Membrane Expansion

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