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Cytosolic chaperones mediate quality control of higher-order septin assembly in budding yeast
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 assemb...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454179/ https://www.ncbi.nlm.nih.gov/pubmed/25673805 http://dx.doi.org/10.1091/mbc.E14-11-1531 |
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author | Johnson, Courtney R. Weems, Andrew D. Brewer, Jennifer M. Thorner, Jeremy McMurray, Michael A. |
author_facet | Johnson, Courtney R. Weems, Andrew D. Brewer, Jennifer M. Thorner, Jeremy McMurray, Michael A. |
author_sort | Johnson, Courtney R. |
collection | PubMed |
description | 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. Unexpectedly, 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. |
format | Online Article Text |
id | pubmed-4454179 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-44541792015-06-16 Cytosolic chaperones mediate quality control of higher-order septin assembly in budding yeast Johnson, Courtney R. Weems, Andrew D. Brewer, Jennifer M. Thorner, Jeremy McMurray, Michael A. Mol Biol Cell Articles 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. Unexpectedly, 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. The American Society for Cell Biology 2015-04-01 /pmc/articles/PMC4454179/ /pubmed/25673805 http://dx.doi.org/10.1091/mbc.E14-11-1531 Text en © 2015 Johnson et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Johnson, Courtney R. Weems, Andrew D. Brewer, Jennifer M. Thorner, Jeremy McMurray, Michael A. Cytosolic chaperones mediate quality control of higher-order septin assembly in budding yeast |
title | Cytosolic chaperones mediate quality control of higher-order septin assembly in budding yeast |
title_full | Cytosolic chaperones mediate quality control of higher-order septin assembly in budding yeast |
title_fullStr | Cytosolic chaperones mediate quality control of higher-order septin assembly in budding yeast |
title_full_unstemmed | Cytosolic chaperones mediate quality control of higher-order septin assembly in budding yeast |
title_short | Cytosolic chaperones mediate quality control of higher-order septin assembly in budding yeast |
title_sort | cytosolic chaperones mediate quality control of higher-order septin assembly in budding yeast |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454179/ https://www.ncbi.nlm.nih.gov/pubmed/25673805 http://dx.doi.org/10.1091/mbc.E14-11-1531 |
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