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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Published in:Frontiers in cell and developmental biology 2022-03, Vol.10, p.878027-878027
Main Authors: Poschmann, Gereon, Bahr, Jasmin, Schrader, Jürgen, Stejerean-Todoran, Ioana, Bogeski, Ivan, Stühler, Kai
Format: Article
Language:English
Subjects:
Cell and Developmental Biology
comparative secretomics
high-confident secretome (Min.5-Max. 8)
mass spectrometry
pharmacosecretomics
Secretome
unconventional protein secretion
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Summary: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.
ISSN:2296-634X
2296-634X
DOI:10.3389/fcell.2022.878027