Fusion of Protein Aggregates Facilitates Asymmetric Damage Segregation

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Miguel Coelho - , Max Planck Institute of Molecular Cell Biology and Genetics, Harvard University (Autor:in)
  • Steven J. Lade - , Max-Planck-Institut für Physik komplexer Systeme, Stockholm University (Autor:in)
  • Simon Alberti - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Thilo Gross - , Max-Planck-Institut für Physik komplexer Systeme, University of Bristol (Autor:in)
  • Iva M. Tolić - , Max Planck Institute of Molecular Cell Biology and Genetics, Ruđer Bošković Institute (Autor:in)

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.

Details

OriginalspracheEnglisch
Aufsatznummere1001886
Seiten (von - bis)1-11
Seitenumfang11
FachzeitschriftPLoS biology
Jahrgang12
Ausgabenummer6
PublikationsstatusVeröffentlicht - 2014
Peer-Review-StatusJa
Extern publiziertJa

Externe IDs

PubMed 24936793
ORCID /0000-0003-4017-6505/work/142253881