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Cytosolic aggregates perturb the degradation of nontranslocated secretory and membrane proteins
A wide range of diseases are associated with the accumulation of cytosolic protein aggregates. The effects of these aggregates on various aspects of normal cellular protein homeostasis remain to be determined. Here we find that cytosolic aggregates, without necessarily disrupting proteasome function...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
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The American Society for Cell Biology
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093316/ https://www.ncbi.nlm.nih.gov/pubmed/21411629 http://dx.doi.org/10.1091/mbc.E10-07-0638 |
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author | Chakrabarti, Oishee Rane, Neena S. Hegde, Ramanujan S. |
author_facet | Chakrabarti, Oishee Rane, Neena S. Hegde, Ramanujan S. |
author_sort | Chakrabarti, Oishee |
collection | PubMed |
description | A wide range of diseases are associated with the accumulation of cytosolic protein aggregates. The effects of these aggregates on various aspects of normal cellular protein homeostasis remain to be determined. Here we find that cytosolic aggregates, without necessarily disrupting proteasome function, can markedly delay the normally rapid degradation of nontranslocated secretory and membrane protein precursors. In the case of mammalian prion protein (PrP), the nontranslocated fraction is recruited into preexisting aggregates before its triage for degradation. This recruitment permits the growth and persistence of cytosolic PrP aggregates, explaining their apparent “self-conversion” seen in earlier studies of transient proteasome inhibition. For other proteins, the aggregate-mediated delay in precursor degradation led to aggregation and/or soluble residence in the cytosol, often causing aberrant cellular morphology. Remarkably, improving signal sequence efficiency mitigated these effects of aggregates. These observations identify a previously unappreciated consequence of cytosolic aggregates for nontranslocated secretory and membrane proteins, a minor but potentially disruptive population the rapid disposal of which is critical to maintaining cellular homeostasis. |
format | Text |
id | pubmed-3093316 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-30933162011-07-30 Cytosolic aggregates perturb the degradation of nontranslocated secretory and membrane proteins Chakrabarti, Oishee Rane, Neena S. Hegde, Ramanujan S. Mol Biol Cell Articles A wide range of diseases are associated with the accumulation of cytosolic protein aggregates. The effects of these aggregates on various aspects of normal cellular protein homeostasis remain to be determined. Here we find that cytosolic aggregates, without necessarily disrupting proteasome function, can markedly delay the normally rapid degradation of nontranslocated secretory and membrane protein precursors. In the case of mammalian prion protein (PrP), the nontranslocated fraction is recruited into preexisting aggregates before its triage for degradation. This recruitment permits the growth and persistence of cytosolic PrP aggregates, explaining their apparent “self-conversion” seen in earlier studies of transient proteasome inhibition. For other proteins, the aggregate-mediated delay in precursor degradation led to aggregation and/or soluble residence in the cytosol, often causing aberrant cellular morphology. Remarkably, improving signal sequence efficiency mitigated these effects of aggregates. These observations identify a previously unappreciated consequence of cytosolic aggregates for nontranslocated secretory and membrane proteins, a minor but potentially disruptive population the rapid disposal of which is critical to maintaining cellular homeostasis. The American Society for Cell Biology 2011-05-15 /pmc/articles/PMC3093316/ /pubmed/21411629 http://dx.doi.org/10.1091/mbc.E10-07-0638 Text en © 2011 Chakrabarti 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 of Cell Biology. |
spellingShingle | Articles Chakrabarti, Oishee Rane, Neena S. Hegde, Ramanujan S. Cytosolic aggregates perturb the degradation of nontranslocated secretory and membrane proteins |
title | Cytosolic aggregates perturb the degradation of nontranslocated secretory and membrane proteins |
title_full | Cytosolic aggregates perturb the degradation of nontranslocated secretory and membrane proteins |
title_fullStr | Cytosolic aggregates perturb the degradation of nontranslocated secretory and membrane proteins |
title_full_unstemmed | Cytosolic aggregates perturb the degradation of nontranslocated secretory and membrane proteins |
title_short | Cytosolic aggregates perturb the degradation of nontranslocated secretory and membrane proteins |
title_sort | cytosolic aggregates perturb the degradation of nontranslocated secretory and membrane proteins |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093316/ https://www.ncbi.nlm.nih.gov/pubmed/21411629 http://dx.doi.org/10.1091/mbc.E10-07-0638 |
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