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Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation
Mammalian cells secrete a large number of small proteins, but their mode of translocation into the endoplasmic reticulum is not fully understood. Cotranslational translocation was expected to be inefficient due to the small time window for signal sequence recognition by the signal recognition partic...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395660/ https://www.ncbi.nlm.nih.gov/pubmed/22648169 http://dx.doi.org/10.1091/mbc.E12-03-0228 |
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author | Lakkaraju, Asvin K. K. Thankappan, Ratheeshkumar Mary, Camille Garrison, Jennifer L. Taunton, Jack Strub, Katharina |
author_facet | Lakkaraju, Asvin K. K. Thankappan, Ratheeshkumar Mary, Camille Garrison, Jennifer L. Taunton, Jack Strub, Katharina |
author_sort | Lakkaraju, Asvin K. K. |
collection | PubMed |
description | Mammalian cells secrete a large number of small proteins, but their mode of translocation into the endoplasmic reticulum is not fully understood. Cotranslational translocation was expected to be inefficient due to the small time window for signal sequence recognition by the signal recognition particle (SRP). Impairing the SRP pathway and reducing cellular levels of the translocon component Sec62 by RNA interference, we found an alternate, Sec62-dependent translocation path in mammalian cells required for the efficient translocation of small proteins with N-terminal signal sequences. The Sec62-dependent translocation occurs posttranslationally via the Sec61 translocon and requires ATP. We classified preproteins into three groups: 1) those that comprise ≤100 amino acids are strongly dependent on Sec62 for efficient translocation; 2) those in the size range of 120–160 amino acids use the SRP pathway, albeit inefficiently, and therefore rely on Sec62 for efficient translocation; and 3) those larger than 160 amino acids depend on the SRP pathway to preserve a transient translocation competence independent of Sec62. Thus, unlike in yeast, the Sec62-dependent translocation pathway in mammalian cells serves mainly as a fail-safe mechanism to ensure efficient secretion of small proteins and provides cells with an opportunity to regulate secretion of small proteins independent of the SRP pathway. |
format | Online Article Text |
id | pubmed-3395660 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-33956602012-09-30 Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation Lakkaraju, Asvin K. K. Thankappan, Ratheeshkumar Mary, Camille Garrison, Jennifer L. Taunton, Jack Strub, Katharina Mol Biol Cell Articles Mammalian cells secrete a large number of small proteins, but their mode of translocation into the endoplasmic reticulum is not fully understood. Cotranslational translocation was expected to be inefficient due to the small time window for signal sequence recognition by the signal recognition particle (SRP). Impairing the SRP pathway and reducing cellular levels of the translocon component Sec62 by RNA interference, we found an alternate, Sec62-dependent translocation path in mammalian cells required for the efficient translocation of small proteins with N-terminal signal sequences. The Sec62-dependent translocation occurs posttranslationally via the Sec61 translocon and requires ATP. We classified preproteins into three groups: 1) those that comprise ≤100 amino acids are strongly dependent on Sec62 for efficient translocation; 2) those in the size range of 120–160 amino acids use the SRP pathway, albeit inefficiently, and therefore rely on Sec62 for efficient translocation; and 3) those larger than 160 amino acids depend on the SRP pathway to preserve a transient translocation competence independent of Sec62. Thus, unlike in yeast, the Sec62-dependent translocation pathway in mammalian cells serves mainly as a fail-safe mechanism to ensure efficient secretion of small proteins and provides cells with an opportunity to regulate secretion of small proteins independent of the SRP pathway. The American Society for Cell Biology 2012-07-15 /pmc/articles/PMC3395660/ /pubmed/22648169 http://dx.doi.org/10.1091/mbc.E12-03-0228 Text en © 2012 Lakkaraju 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 BD; are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Lakkaraju, Asvin K. K. Thankappan, Ratheeshkumar Mary, Camille Garrison, Jennifer L. Taunton, Jack Strub, Katharina Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation |
title | Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation |
title_full | Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation |
title_fullStr | Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation |
title_full_unstemmed | Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation |
title_short | Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation |
title_sort | efficient secretion of small proteins in mammalian cells relies on sec62-dependent posttranslational translocation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395660/ https://www.ncbi.nlm.nih.gov/pubmed/22648169 http://dx.doi.org/10.1091/mbc.E12-03-0228 |
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