Format

Send to

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 2014 Oct 3;289(40):27625-39. doi: 10.1074/jbc.M114.582429. Epub 2014 Aug 20.

Stress-dependent proteolytic processing of the actin assembly protein Lsb1 modulates a yeast prion.

Author information

1
From the Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322.
2
From the Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, tcherno@emory.edu.
3
the School of Biology and Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332.
4
the Center for Cancer Research Core Fluorescence Imaging Facility, Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
5
the Division of Microbiology, Yerkes Research Center, Emory University, Atlanta, Georgia 30329, and.
6
the School of Biology and Parker H. Petit Institute for Bioengineering & Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, the Laboratory of Amyloid Biology, St. Petersburg State University, St. Petersburg, Russia 199034.
7
From the Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, genekdw@emory.edu.

Abstract

Yeast prions are self-propagating amyloid-like aggregates of Q/N-rich protein that confer heritable traits and provide a model of mammalian amyloidoses. [PSI(+)] is a prion isoform of the translation termination factor Sup35. Propagation of [PSI(+)] during cell division under normal conditions and during the recovery from damaging environmental stress depends on cellular chaperones and is influenced by ubiquitin proteolysis and the actin cytoskeleton. The paralogous yeast proteins Lsb1 and Lsb2 bind the actin assembly protein Las17 (a yeast homolog of human Wiskott-Aldrich syndrome protein) and participate in the endocytic pathway. Lsb2 was shown to modulate maintenance of [PSI(+)] during and after heat shock. Here, we demonstrate that Lsb1 also regulates maintenance of the Sup35 prion during and after heat shock. These data point to the involvement of Lsb proteins in the partitioning of protein aggregates in stressed cells. Lsb1 abundance and cycling between actin patches, endoplasmic reticulum, and cytosol is regulated by the Guided Entry of Tail-anchored proteins pathway and Rsp5-dependent ubiquitination. Heat shock-induced proteolytic processing of Lsb1 is crucial for prion maintenance during stress. Our findings identify Lsb1 as another component of a tightly regulated pathway controlling protein aggregation in changing environments.

KEYWORDS:

Actin; Endoplasmic Reticulum (ER); Heat Shock; Prion; Proteasome; Rsp5; Sup35; Ubiquitylation (Ubiquitination)

PMID:
25143386
PMCID:
PMC4183801
DOI:
10.1074/jbc.M114.582429
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center