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Yeast ceramide synthases, Lag1 and Lac1, have distinct substrate specificity

Publié dansJournal of Cell Science, vol. 132, no. jcs228411
Date de publication2019
Résumé

LAG1 was the first longevity assurance gene discovered in Saccharomyces cerevisiae. The Lag1 protein is a ceramide synthase and its homolog, Lac1, has a similar enzymatic function but no role in aging. Lag1 and Lac1 lie in an enzymatic branch point of the sphingolipid pathway that is interconnected by the activity of the C4 hydroxylase, Sur2. By uncoupling the enzymatic branch point and using lipidomic mass spectrometry, metabolic labeling and in vitro assays we show that Lag1 preferentially synthesizes phyto-sphingolipids. Using photo-bleaching experiments we show that Lag1 is uniquely required for the establishment of a lateral diffusion barrier in the nuclear envelope, which depends on phytoceramide. Given the role of this diffusion barrier in the retention of aging factors in the mother cell, we suggest that the different specificities of the two ceramide synthases, and the specific effect of Lag1 on asymmetrical inheritance, may explain why Δlag1 cells have an increased lifespan while Δlac1 cells do not.

Mots-clés
  • Yeast
  • Saccharomyces cerevisiae
  • Lag1
  • Lac1
  • Phytoceramide
  • Dihydroceramide
  • Ceramide synthases
  • Aging
Citation (format ISO)
MEGYERI, Márton et al. Yeast ceramide synthases, Lag1 and Lac1, have distinct substrate specificity. In: Journal of Cell Science, 2019, vol. 132, n° jcs228411. doi: 10.1242/jcs.228411
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Article (Published version)
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Identifiants
ISSN du journal0021-9533
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Informations techniques

Création15/09/2020 16:35:00
Première validation15/09/2020 16:35:00
Heure de mise à jour15/03/2023 22:37:02
Changement de statut15/03/2023 22:37:00
Dernière indexation17/01/2024 10:53:49
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