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Mol Biol Cell. 2017 Oct 1;28(20):2712-2722. doi: 10.1091/mbc.E17-05-0335. Epub 2017 Aug 2.

Sphingolipids facilitate age asymmetry of membrane proteins in dividing yeast cells.

Singh P1,2, Ramachandran SK1,2, Zhu J1,2, Kim BC3,4,5,6, Biswas D7, Ha T3,4,5, Iglesias PA1,4,7, Li R8,2.

Author information

1
Center for Cell Dynamics, Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
2
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218.
3
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, MD 21205.
4
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218.
5
Howard Hughes Medical Institute, Baltimore, MD 21218.
6
Division of Nano-bioengineering, Incheon National University, Incheon 22012, Republic of Korea.
7
Electrical and Computer Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218.
8
Center for Cell Dynamics, Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 rong@jhu.edu.

Abstract

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.

PMID:
28768828
PMCID:
PMC5620378
DOI:
10.1091/mbc.E17-05-0335
[Indexed for MEDLINE]
Free PMC Article

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