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Curr Biol. 2017 Mar 20;27(6):773-783. doi: 10.1016/j.cub.2017.01.069. Epub 2017 Mar 2.

Compartmentalization of ER-Bound Chaperone Confines Protein Deposit Formation to the Aging Yeast Cell.

Author information

1
Institute of Biochemistry, ETH Zurich, Otto-Stern-Weg 3, 8093 Zurich, Switzerland; Wissenschaftskolleg zu Berlin, Institute for Advanced Study, Wallotstrasse 19, 14193 Berlin, Germany.
2
Institute of Biochemistry, ETH Zurich, Otto-Stern-Weg 3, 8093 Zurich, Switzerland; Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.
3
Institute of Biochemistry, ETH Zurich, Otto-Stern-Weg 3, 8093 Zurich, Switzerland.
4
Molecular Biology Institute of Barcelona, CSIC, Baldiri i Reixac 15, 08028 Barcelona, Spain.
5
Institute of Biochemistry, ETH Zurich, Otto-Stern-Weg 3, 8093 Zurich, Switzerland. Electronic address: yves.barral@bc.biol.ethz.ch.

Abstract

In order to produce rejuvenated daughters, dividing budding yeast cells confine aging factors, including protein aggregates, to the aging mother cell. The asymmetric inheritance of these protein deposits is mediated by organelle and cytoskeletal attachment and by cell geometry. Yet it remains unclear how deposit formation is restricted to the aging lineage. Here, we show that selective membrane anchoring and the compartmentalization of the endoplasmic reticulum (ER) membrane confine protein deposit formation to aging cells during division. Supporting the idea that the age-dependent deposit forms through coalescence of smaller aggregates, two deposits rapidly merged when placed in the same cell by cell-cell fusion. The deposits localized to the ER membrane, primarily to the nuclear envelope (NE). Strikingly, weakening the diffusion barriers that separate the ER membrane into mother and bud compartments caused premature formation of deposits in the daughter cells. Detachment of the Hsp40 protein Ydj1 from the ER membrane elicited a similar phenotype, suggesting that the diffusion barriers and farnesylated Ydj1 functioned together to confine protein deposit formation to mother cells during division. Accordingly, fluorescence correlation spectroscopy measurements in dividing cells indicated that a slow-diffusing, possibly client-bound Ydj1 fraction was asymmetrically enriched in the mother compartment. This asymmetric distribution depended on Ydj1 farnesylation and intact diffusion barriers. Taking these findings together, we propose that ER-anchored Ydj1 binds deposit precursors and prevents them from spreading into daughter cells during division by subjecting them to the ER diffusion barriers. This ensures that the coalescence of precursors into a single deposit is restricted to the aging lineage.

KEYWORDS:

DnaJ; Sup35; aggregate seed; asymmetric division; diffusion barrier; farnesylation; prenylation; prion

PMID:
28262489
DOI:
10.1016/j.cub.2017.01.069
[Indexed for MEDLINE]
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