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PMID: 25673805 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Cytosolic chaperones mediate quality control of higher-order septin assembly in budding yeast.

Molecular biology of the cell ·Vol. 26 ·No. 7 ·2015-04-01 ·Pages 1323-44

Johnson CR, Weems AD, Brewer JM, Thorner J, McMurray MA

Abstract

Septin hetero-oligomers polymerize into cytoskeletal filaments with essential functions in many eukaryotic cell types. Mutations within the oligomerization interface that encompasses the GTP-binding pocket of a septin (its "G interface") cause thermoinstability of yeast septin hetero-oligomer assembly, and human disease. When coexpressed with its wild-type counterpart, a G interface mutant is excluded from septin filaments, even at moderate temperatures. We show that this quality control mechanism is specific to G interface mutants, operates during de novo septin hetero-oligomer assembly, and requires specific cytosolic chaperones. Chaperone overexpression lowers the temperature permissive for proliferation of cells expressing a G interface mutant as the sole source of a given septin. Mutations that perturb the septin G interface retard release from these chaperones, imposing a kinetic delay on the availability of nascent septin molecules for higher-order assembly. Un-expectedly, the disaggregase Hsp104 contributes to this delay in a manner that does not require its "unfoldase" activity, indicating a latent "holdase" activity toward mutant septins. These findings provide new roles for chaperone-mediated kinetic partitioning of non-native proteins and may help explain the etiology of septin-linked human diseases.

MeSH Terms
Alleles Cytoskeleton/metabolism HSP40 Heat-Shock Proteins/metabolism Heat-Shock Proteins/metabolism Molecular Chaperones/metabolism Mutation Protein Multimerization Saccharomyces cerevisiae/metabolism Saccharomyces cerevisiae Proteins/metabolism Septins/genetics,metabolism
Chemicals
HSP40 Heat-Shock Proteins Heat-Shock Proteins Molecular Chaperones Saccharomyces cerevisiae Proteins YDJ1 protein, S cerevisiae HsP104 protein, S cerevisiae Septins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Johnson Courtney R
Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
Weems Andrew D
Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
Brewer Jennifer M
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720.
Thorner Jeremy
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720.
McMurray Michael A
Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 [email protected].
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1939-4586
DOI
10.1091/mbc.E14-11-1531
Email
[email protected]
Published
2015-04-01
Epub
2015-00-11
Pages
1323-44
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC4454179
Subset
IM
Grants
NIGMS NIH HHS · R01 GM021841 · United States
NIGMS NIH HHS · R00GM086603 · United States
NIGMS NIH HHS · K99 GM086603 · United States
NIGMS NIH HHS · R01 GM101314 · United States
NIGMS NIH HHS · R00 GM086603 · United States
NIGMS NIH HHS · R01GM021841 · United States
External Links
PubMed source DOI: 10.1091/mbc.E14-11-1531 PMC Full Text View journal details
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