Get3 is a holdase chaperone and moves to deposition sites for aggregated proteins when membrane targeting is blocked

Katie Powis, Bianca Schrul, Heather Tienson, Irina Gostimskaya, Michal Breker, Stephen High, Maya Schuldiner, Ursula Jakob, Blanche Schwappach*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

The endomembrane system of yeast contains different tail-anchored proteins that are post-translationally targeted to membranes via their C-terminal transmembrane domain. This hydrophobic segment could be hazardous in the cytosol if membrane insertion fails, resulting in the need for energy-dependent chaperoning and the degradation of aggregated tail-anchored proteins. A cascade of GET proteins cooperates in a conserved pathway to accept newly synthesized tail-anchored proteins from ribosomes and guide them to a receptor at the endoplasmic reticulum, where membrane integration takes place. It is, however, unclear how the GET system reacts to conditions of energy depletion that might prevent membrane insertion and hence lead to the accumulation of hydrophobic proteins in the cytosol. Here we show that the ATPase Get3, which accommodates the hydrophobic tail anchor of clients, has a dual function: promoting tailanchored protein insertion when glucose is abundant and serving as an ATP-independent holdase chaperone during energy depletion. Like the generic chaperones Hsp42, Ssa2, Sis1 and Hsp104, we found that Get3 moves reversibly to deposition sites for protein aggregates, hence supporting the sequestration of tail-anchored proteins under conditions that prevent tail-anchored protein insertion. Our findings support a ubiquitous role for the cytosolic GET complex as a triaging platform involved in cellular proteostasis.

Original languageAmerican English
Pages (from-to)473-483
Number of pages11
JournalJournal of Cell Science
Volume126
Issue number2
DOIs
StatePublished - Jan 2013
Externally publishedYes

Keywords

  • Chaperones
  • GET pathway
  • Glucose starvation
  • Tail-anchored proteins

Fingerprint

Dive into the research topics of 'Get3 is a holdase chaperone and moves to deposition sites for aggregated proteins when membrane targeting is blocked'. Together they form a unique fingerprint.

Cite this