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Sphingolipids facilitate age asymmetry of membrane proteins in dividing yeast cells

One proposed mechanism of cellular aging is the gradual loss of certain cellular components that are insufficiently renewed. In an earlier study, multidrug resistance transporters (MDRs) were postulated to be such aging determinants during the yeast replicative life span (RLS). Aged MDR proteins wer...

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Autores principales: Singh, Pushpendra, Ramachandran, Sree Kumar, Zhu, Jin, Kim, Byoung Choul, Biswas, Debojyoti, Ha, Taekjip, Iglesias, Pablo A., Li, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620378/
https://www.ncbi.nlm.nih.gov/pubmed/28768828
http://dx.doi.org/10.1091/mbc.E17-05-0335
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author Singh, Pushpendra
Ramachandran, Sree Kumar
Zhu, Jin
Kim, Byoung Choul
Biswas, Debojyoti
Ha, Taekjip
Iglesias, Pablo A.
Li, Rong
author_facet Singh, Pushpendra
Ramachandran, Sree Kumar
Zhu, Jin
Kim, Byoung Choul
Biswas, Debojyoti
Ha, Taekjip
Iglesias, Pablo A.
Li, Rong
author_sort Singh, Pushpendra
collection PubMed
description One proposed mechanism of cellular aging is the gradual loss of certain cellular components that are insufficiently renewed. In an earlier study, multidrug resistance transporters (MDRs) were postulated to be such aging determinants during the yeast replicative life span (RLS). Aged MDR proteins were asymmetrically retained by the aging mother cell and did not diffuse freely into the bud, whereas newly synthesized MDR proteins were thought to be deposited mostly in the bud before cytokinesis. In this study, we further demonstrate the proposed age asymmetry of MDR proteins in dividing yeast cells and investigate the mechanism that controls diffusive properties of MDR proteins to maintain this asymmetry. We found that long-chain sphingolipids, but not the septin/endoplasmic reticulum–based membrane diffusion barrier, are important for restricting MDR diffusion. Depletion of sphingolipids or shortening of their long acyl chains resulted in an increase in the lateral mobility of MDR proteins, causing aged MDR protein in the mother cell to enter the bud. We used a mathematical model to understand the effect of diminished MDR age asymmetry on yeast cell aging, the result of which was qualitatively consistent with the observed RLS shortening in sphingolipid mutants.
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spelling pubmed-56203782017-12-16 Sphingolipids facilitate age asymmetry of membrane proteins in dividing yeast cells Singh, Pushpendra Ramachandran, Sree Kumar Zhu, Jin Kim, Byoung Choul Biswas, Debojyoti Ha, Taekjip Iglesias, Pablo A. Li, Rong Mol Biol Cell Articles One proposed mechanism of cellular aging is the gradual loss of certain cellular components that are insufficiently renewed. In an earlier study, multidrug resistance transporters (MDRs) were postulated to be such aging determinants during the yeast replicative life span (RLS). Aged MDR proteins were asymmetrically retained by the aging mother cell and did not diffuse freely into the bud, whereas newly synthesized MDR proteins were thought to be deposited mostly in the bud before cytokinesis. In this study, we further demonstrate the proposed age asymmetry of MDR proteins in dividing yeast cells and investigate the mechanism that controls diffusive properties of MDR proteins to maintain this asymmetry. We found that long-chain sphingolipids, but not the septin/endoplasmic reticulum–based membrane diffusion barrier, are important for restricting MDR diffusion. Depletion of sphingolipids or shortening of their long acyl chains resulted in an increase in the lateral mobility of MDR proteins, causing aged MDR protein in the mother cell to enter the bud. We used a mathematical model to understand the effect of diminished MDR age asymmetry on yeast cell aging, the result of which was qualitatively consistent with the observed RLS shortening in sphingolipid mutants. The American Society for Cell Biology 2017-10-01 /pmc/articles/PMC5620378/ /pubmed/28768828 http://dx.doi.org/10.1091/mbc.E17-05-0335 Text en © 2017 Singh et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Singh, Pushpendra
Ramachandran, Sree Kumar
Zhu, Jin
Kim, Byoung Choul
Biswas, Debojyoti
Ha, Taekjip
Iglesias, Pablo A.
Li, Rong
Sphingolipids facilitate age asymmetry of membrane proteins in dividing yeast cells
title Sphingolipids facilitate age asymmetry of membrane proteins in dividing yeast cells
title_full Sphingolipids facilitate age asymmetry of membrane proteins in dividing yeast cells
title_fullStr Sphingolipids facilitate age asymmetry of membrane proteins in dividing yeast cells
title_full_unstemmed Sphingolipids facilitate age asymmetry of membrane proteins in dividing yeast cells
title_short Sphingolipids facilitate age asymmetry of membrane proteins in dividing yeast cells
title_sort sphingolipids facilitate age asymmetry of membrane proteins in dividing yeast cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620378/
https://www.ncbi.nlm.nih.gov/pubmed/28768828
http://dx.doi.org/10.1091/mbc.E17-05-0335
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