Fusion of Protein Aggregates Facilitates Asymmetric Damage Segregation

Coelho, Miguel; Lade, Steven J.; Alberti, Simon; Gross, Thilo; Tolić, Iva M. (2014) Fusion of Protein Aggregates Facilitates Asymmetric Damage Segregation. PLoS ONE, 12 (6). ISSN 1932-6203

Preview

PDF - Published Version - article Available under License Creative Commons Attribution. Download (909kB) | Preview

Abstract

Asymmetric segregation of damaged proteins at cell division generates a cell that retains damage and a clean cell that supports population survival. In cells that divide asymmetrically, such as Saccharomyces cerevisiae, segregation of damaged proteins is achieved by retention and active transport. We have previously shown that in the symmetrically dividing Schizosaccharomyces pombe there is a transition between symmetric and asymmetric segregation of damaged proteins. Yet how this transition and generation of damage-free cells are achieved remained unknown. Here, by combining in vivo imaging of Hsp104-associated aggregates, a form of damage, with mathematical modeling, we find that fusion of protein aggregates facilitates asymmetric segregation. Our model predicts that, after stress, the increased number of aggregates fuse into a single large unit, which is inherited asymmetrically by one daughter cell, whereas the other one is born clean. We experimentally confirmed that fusion increases segregation asymmetry, for a range of stresses, and identified Hsp16 as a fusion factor. Our work shows that fusion of protein aggregates promotes the formation of damage-free cells. Fusion of cellular factors may represent a general mechanism for their asymmetric segregation at division.

Item Type:	Article
Uncontrolled Keywords:	Cell fusion; Thermal stresses; Damage mechanics; Damage segregation
Subjects:	NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology
Divisions:	Division of Molecular Biology
Depositing User:	Patrik Risteski
Date Deposited:	22 Oct 2015 11:08
URI:	http://fulir.irb.hr/id/eprint/2178
DOI:	10.1371/journal.pbio.1001886

Actions (login required)

View Item