Unconventional protein secretion: The hidden pathways

doi:10.1016/j.bbapap.2019.140272

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

Volume 1867, Issue 12, December 2019, 140272

https://doi.org/10.1016/j.bbapap.2019.140272 Get rights and content

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Cited by (4)

Revealing protein trafficking by proximity labeling-based proteomics
2024, Bioorganic Chemistry
Protein trafficking is a fundamental process with profound implications for both intracellular and intercellular functions. Proximity labeling (PL) technology has emerged as a powerful tool for capturing precise snapshots of subcellular proteomes by directing promiscuous enzymes to specific cellular locations. These enzymes generate reactive species that tag endogenous proteins, enabling their identification through mass spectrometry-based proteomics. In this comprehensive review, we delve into recent advancements in PL-based methodologies, placing particular emphasis on the label-and-fractionation approach and TransitID, for mapping proteome trafficking. These methodologies not only facilitate the exploration of dynamic intracellular protein trafficking between organelles but also illuminate the intricate web of intercellular and inter-organ protein communications.
Identification of secreted proteins by comparison of protein abundance in conditioned media and cell lysates
2022, Analytical Biochemistry
Citation Excerpt :
While the majority of secreted proteins utilize the ER-Golgi secretory vesicle pathway, a subset of cytoplasmic proteins have been shown to be secreted via ER-Golgi independent “unconventional” secretory routes [6–8]. Following synthesis in the cytoplasm, unconventionally secreted proteins, which include some cytokines and angiogenic growth factors, are secreted either through protein conducting pores that form in the plasma membrane, or via vesicular intermediates derived from the auto/endo-lysosomal system [8–10]. Characterizing the entire set of secreted proteins, i.e. the secretome, using cell culture-based model systems has been a long standing challenge [2].
Analysis of the full spectrum of secreted proteins in cell culture is complicated by leakage of intracellular proteins from damaged cells. To address this issue, we compared the abundance of individual proteins between the cell lysate and the conditioned medium, reasoning that secreted proteins should be relatively more abundant in the conditioned medium. Marked enrichment for signal-peptide-bearing proteins with increasing conditioned media to cell lysate ratio, as well loss of this signal following brefeldin A treatment, confirmed the sensitivity and specificity of this approach. The subset of proteins demonstrating increased conditioned media to cell lysate ratio in the presence of Brefeldin A identified candidates for unconventional secretion via a pathway independent of ER to Golgi trafficking.
PKG II secreted via the classical endoplasmic reticulum–Golgi apparatus secretory pathway blocks the activation of EGFR through phosporalting its threonine 406 and has an anti-tumor effect
2022, Frontiers in Bioscience - Landmark
Monitoring the levels of cellular nf-κb activation states
2021, Cancers

Kai Stühler, studied chemistry and microbiological chemistry and received his diploma degree in 1999 at the University Wuppertal, Germany. Under the supervision of Prof. Dr. Helmut E. Meyer he acquired his PhD analysing the function of tumor suppressor Smad4 in gastrointestinal cell lines at the Ruhr-Universität Bochum, Germany in 2003. From 2004 to 2009 he was leader of the young scientist group Neuroproteomics supported by the Ministry of Science and Research North Rhine Westphalia. During this time, he was mainly interested in biomarker discovery and soon realized that it was also important to study how protein-biomarkers are released e.g. into the bloodstream. Since 2004 - when he published his first secretome of coloncarcinoma cells – he constantly worked on the topic of protein secretion and found that mass spectrometry based proteomics is an excellent tool for characterizing secretomes and the underlying mechanism of secretion. Since 2011 Kai Stühler is the head of the Molecular Proteomics Laboratory at Heinrich-Heine-University in Düsseldorf and has a professorship in proteome research. In Düsseldorf he continues his work on secretome analysis covering experimental work as well as theoretical aspects like the prediction of classically and unconventional secreted proteins.

Kerstin Schipper is a group leader in the Institute for Microbiology at Heinrich Heine University Düsseldorf, Germany. She performed her doctoral studies in Prof. Regine Kahmanns lab at the Max Planck Institute for Terrestrial Microbiology in Marburg and received her PhD in plant pathogen interactions in 2009 from the Philipps University. At that time she studied pathogen effectors and became fascinated by protein secretion. Her group in Düsseldorf is interested in a novel mechanism of unconventional protein secretion in the corn smut Ustilago maydis. Besides characterizing the molecular details of the secretory mechanism, her group is also engaged in its application for heterologous protein secretion.

Gereon Poschmann received his PhD in 2004 form the faculty of biology at the Ruhr-Universität Bochum, Germany. For his postdoctoral studies he joined the laboratory of Prof. Dr. Helmut E. Meyer from 2005 to 2011. During these years, he got familiar with protein analysis and mass spectrometry and realized the big potential of these techniques for answering biological question. One focus of his work in Bochum was biomarker discovery and validation. In 2012 he moved to the Molecular Proteomics Laboratory at the Heinrich Heine University Düsseldorf (headed by Prof. Dr. Kai Stühler) where he established his own research group focused on understanding protein related redox processes and their analysis by mass spectrometry based techniques.

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EditorialUnconventional protein secretion: The hidden pathways

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Editorial
Unconventional protein secretion: The hidden pathways