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[PMID]: | 27524515 |
[Au] Autor: | James AW; Gowsalya R; Nachiappan V |
[Ad] Endereço: | Biomembrane Lab, Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu, India. |
[Ti] Título: | Dolichyl pyrophosphate phosphatase-mediated N-glycosylation defect dysregulates lipid homeostasis in Saccharomyces cerevisiae. |
[So] Source: | Biochim Biophys Acta;1861(11):1705-1718, 2016 Nov. | [Is] ISSN: | 0006-3002 |
[Cp] País de publicação: | Netherlands |
[La] Idioma: | eng |
[Ab] Resumo: | The endoplasmic reticulum (ER) has numerous biological functions including protein synthesis, protein folding, and lipid synthesis. The CAX4 gene encodes dolichyl pyrophosphate (Dol-PP) phosphatase, which is involved in protein N-glycosylation. In cax4Δ cells, the N-glycosylation of the vacuolar carboxypeptidase (CPY) was severely affected, and expression of the ER chaperone Kar2p was elevated, which resulted in UPR activation as an adaptive response. The cax4Δ cell growth was reduced, and this could be attributed to the formation of clumped aggregates, high vesiculation of the intracellular membrane, and plasma membrane alterations were depicted using DiOC6 fluorescence. In the cax4 deletion strain, the transcription factors INO2 and INO4 were upregulated, and the negative regulator OPI1 was concomitantly down regulated, which led to the derepression of the phospholipid genes CHO2, OPI3, PSD1, and PSD2 and resulted in increased phospholipid levels. However, the TAG, SE, and LD levels were significantly reduced, and FFA, sterol, and DAG levels were increased. These findings could be attributed to the derepression of the TAG and SE lipases TGL3, TGL4, TGL5, YEH1, and YEH2 and the repression of LRO1, DGA1, ARE1, and ARE2 in cax4Δ cells. Interestingly, the overexpression of SEC59 or CAX4 in cax4Δ cells prevented the ER stress and growth defect, and restored normal level of phospholipids, neutral lipids, and LDs. The current study revealed the disruption of N-glycosylation-induced ER stress, altered lipid homeostasis accounts for pleiotropic phenotype. Thus, CAX4 regulates membrane biogenesis by coordinating lipid homeostasis with protein quality control. |
[Mh] Termos MeSH primário: |
Fosfatos de Dolicol/metabolismo Homeostase Metabolismo dos Lipídeos Pirofosfatases/metabolismo Proteínas de Saccharomyces cerevisiae/metabolismo Saccharomyces cerevisiae/enzimologia
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[Mh] Termos MeSH secundário: |
Western Blotting Catepsina A/metabolismo Membrana Celular/metabolismo Estresse do Retículo Endoplasmático Fluorescência Regulação Fúngica da Expressão Gênica Genes Fúngicos Teste de Complementação Genética Glicosilação Proteínas de Fluorescência Verde/metabolismo Gotículas Lipídicas/metabolismo Metabolismo dos Lipídeos/genética Mutação/genética Fenótipo Fosfolipídeos/metabolismo Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo RNA Mensageiro/genética RNA Mensageiro/metabolismo Saccharomyces cerevisiae/genética Saccharomyces cerevisiae/crescimento & desenvolvimento Fatores de Tempo Resposta a Proteínas não Dobradas
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (CAX4 protein, S cerevisiae); 0 (Dolichol Phosphates); 0 (Phospholipids); 0 (RNA, Messenger); 0 (Saccharomyces cerevisiae Proteins); 147336-22-9 (Green Fluorescent Proteins); 37247-98-6 (dolichol pyrophosphate); EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor)); EC 2.7.1.108 (dolichol kinase); EC 3.4.16.5 (Cathepsin A); EC 3.6.1.- (Pyrophosphatases) |
[Em] Mês de entrada: | 1711 |
[Cu] Atualização por classe: | 171103 |
[Lr] Data última revisão:
| 171103 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 160816 |
[St] Status: | MEDLINE |
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