The Protease Ste24 Clears Clogged Translocons

Tslil Ast, Susan Michaelis, Maya Schuldiner

Research output: Contribution to journalArticle

Abstract

Summary Translocation into the endoplasmic reticulum (ER) is the first step in the biogenesis of thousands of eukaryotic endomembrane proteins. Although functional ER translocation has been avidly studied, little is known about the quality control mechanisms that resolve faulty translocational states. One such faulty state is translocon clogging, in which the substrate fails to properly translocate and obstructs the translocon pore. To shed light on the machinery required to resolve clogging, we carried out a systematic screen in Saccharomyces cerevisiae that highlighted a role for the ER metalloprotease Ste24. We could demonstrate that Ste24 approaches the translocon upon clogging, and it interacts with and generates cleavage fragments of the clogged protein. Importantly, these functions are conserved in the human homolog, ZMPSTE24, although disease-associated mutant forms of ZMPSTE24 fail to clear the translocon. These results shed light on a new and critical task of Ste24, which safeguards the essential process of translocation.

Original languageEnglish (US)
Pages (from-to)103-114
Number of pages12
JournalCell
Volume164
Issue number1-2
DOIs
StatePublished - Jan 14 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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