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Secretomics—A Key to a Comprehensive Picture of Unconventional Protein Secretion

For a long time, leaderless secreted proteins (LLSP) were neglected as artifacts derived from dying cells. It is now generally accepted that secretion of LLSP–as a part of the collective term unconventional protein secretion (UPS) - is an evolutionarily conserved process and that these LLSP are acti...

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Autores principales: Poschmann, Gereon, Bahr, Jasmin, Schrader, Jürgen, Stejerean-Todoran, Ioana, Bogeski, Ivan, Stühler, Kai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980719/
https://www.ncbi.nlm.nih.gov/pubmed/35392176
http://dx.doi.org/10.3389/fcell.2022.878027
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author Poschmann, Gereon
Bahr, Jasmin
Schrader, Jürgen
Stejerean-Todoran, Ioana
Bogeski, Ivan
Stühler, Kai
author_facet Poschmann, Gereon
Bahr, Jasmin
Schrader, Jürgen
Stejerean-Todoran, Ioana
Bogeski, Ivan
Stühler, Kai
author_sort Poschmann, Gereon
collection PubMed
description For a long time, leaderless secreted proteins (LLSP) were neglected as artifacts derived from dying cells. It is now generally accepted that secretion of LLSP–as a part of the collective term unconventional protein secretion (UPS) - is an evolutionarily conserved process and that these LLSP are actively and selectively secreted from living cells bypassing the classical endoplasmic reticulum-Golgi pathway. However, the mechanism of UPS pathways, as well as the number of LLSP and which part of a protein is involved in the selection of LLSPs for secretion, are still enigmatic and await clarification. Secretomics-a proteomics-based approach to identify and quantify all proteins secreted by a cell-is inherently unbiased toward a particular secretion pathway and offers the opportunity to shed light on the UPS. Here, we will evaluate and present recent results of proteomic workflows allowing to obtain high-confident secretome data. Additionally, we address that cell culture conditions largely affect the composition of the secretome. This has to be kept in mind to control cell culture induced artifacts and adaptation stress in serum free conditions. Evaluation of click chemistry for secretome analysis of cells under serum-containing conditions showed a significant change in the cellular proteome with longer incubation time upon treatment with non-canonical amino acid azidohomoalanine. Finally, we showed that the number of LLSP far exceeds the number of secreted proteins annotated in Uniprot and ProteinAtlas. Thus, secretomics in combination with sophisticated microbioanalytical and sample preparation methods is well suited to provide a comprehensive picture of UPS.
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spelling pubmed-89807192022-04-06 Secretomics—A Key to a Comprehensive Picture of Unconventional Protein Secretion Poschmann, Gereon Bahr, Jasmin Schrader, Jürgen Stejerean-Todoran, Ioana Bogeski, Ivan Stühler, Kai Front Cell Dev Biol Cell and Developmental Biology For a long time, leaderless secreted proteins (LLSP) were neglected as artifacts derived from dying cells. It is now generally accepted that secretion of LLSP–as a part of the collective term unconventional protein secretion (UPS) - is an evolutionarily conserved process and that these LLSP are actively and selectively secreted from living cells bypassing the classical endoplasmic reticulum-Golgi pathway. However, the mechanism of UPS pathways, as well as the number of LLSP and which part of a protein is involved in the selection of LLSPs for secretion, are still enigmatic and await clarification. Secretomics-a proteomics-based approach to identify and quantify all proteins secreted by a cell-is inherently unbiased toward a particular secretion pathway and offers the opportunity to shed light on the UPS. Here, we will evaluate and present recent results of proteomic workflows allowing to obtain high-confident secretome data. Additionally, we address that cell culture conditions largely affect the composition of the secretome. This has to be kept in mind to control cell culture induced artifacts and adaptation stress in serum free conditions. Evaluation of click chemistry for secretome analysis of cells under serum-containing conditions showed a significant change in the cellular proteome with longer incubation time upon treatment with non-canonical amino acid azidohomoalanine. Finally, we showed that the number of LLSP far exceeds the number of secreted proteins annotated in Uniprot and ProteinAtlas. Thus, secretomics in combination with sophisticated microbioanalytical and sample preparation methods is well suited to provide a comprehensive picture of UPS. Frontiers Media S.A. 2022-03-22 /pmc/articles/PMC8980719/ /pubmed/35392176 http://dx.doi.org/10.3389/fcell.2022.878027 Text en Copyright © 2022 Poschmann, Bahr, Schrader, Stejerean-Todoran, Bogeski and Stühler. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Poschmann, Gereon
Bahr, Jasmin
Schrader, Jürgen
Stejerean-Todoran, Ioana
Bogeski, Ivan
Stühler, Kai
Secretomics—A Key to a Comprehensive Picture of Unconventional Protein Secretion
title Secretomics—A Key to a Comprehensive Picture of Unconventional Protein Secretion
title_full Secretomics—A Key to a Comprehensive Picture of Unconventional Protein Secretion
title_fullStr Secretomics—A Key to a Comprehensive Picture of Unconventional Protein Secretion
title_full_unstemmed Secretomics—A Key to a Comprehensive Picture of Unconventional Protein Secretion
title_short Secretomics—A Key to a Comprehensive Picture of Unconventional Protein Secretion
title_sort secretomics—a key to a comprehensive picture of unconventional protein secretion
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980719/
https://www.ncbi.nlm.nih.gov/pubmed/35392176
http://dx.doi.org/10.3389/fcell.2022.878027
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