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

Authors
  • Megyeri, Márton1, 2
  • Prasad, Rupali3
  • Volpert, Giora2
  • Sliwa-Gonzalez, Andrzej3
  • Haribowo, A Galih4
  • Aguilera-Romero, Auxiliadora4
  • Riezman, Howard4
  • Barral, Yves5
  • Futerman, Anthony H6
  • Schuldiner, Maya7
  • 1 Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel. , (Israel)
  • 2 Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel. , (Israel)
  • 3 Institute of Biochemistry, Department of Biology, ETH Zürich, Zürich 8093, Switzerland. , (Switzerland)
  • 4 Department of Biochemistry and NCCR Chemical Biology, University of Geneva, Geneva 1211, Switzerland. , (Switzerland)
  • 5 Institute of Biochemistry, Department of Biology, ETH Zürich, Zürich 8093, Switzerland [email protected] [email protected] [email protected] , (Switzerland)
  • 6 Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel [email protected] [email protected] [email protected] , (Israel)
  • 7 Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel [email protected] [email protected] [email protected] , (Israel)
Type
Published Article
Journal
Journal of Cell Science
Publisher
The Company of Biologists
Publication Date
Jun 24, 2019
Volume
132
Issue
12
Identifiers
DOI: 10.1242/jcs.228411
PMID: 31164445
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. © 2019. Published by The Company of Biologists Ltd.

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