Open AccessComprehensive palmitoyl‐proteomic analysis identifies distinct protein signatures for large and small cancer‐derived extracellular vesicles
Author(s) -
Mariscal Javier,
Vagner Tatyana,
Kim Minhyung,
Zhou Bo,
Chin Andrew,
Zandian Mandana,
Freeman Michael R.,
You Sungyong,
Zijlstra Andries,
Yang Wei,
Di Vizio Dolores
Publication year - 2020
Publication title -
journal of extracellular vesicles
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.94
H-Index - 68
ISSN - 2001-3078
DOI - 10.1080/20013078.2020.1764192
Subject(s) - palmitoylation , proteomics , proteome , microvesicles , extracellular vesicles , biogenesis , biology , microvesicle , protein subcellular localization prediction , human proteome project , microbiology and biotechnology , proteogenomics , computational biology , protein targeting , membrane protein , bioinformatics , biochemistry , microrna , gene , transcriptome , gene expression , cysteine , membrane , enzyme
Extracellular vesicles (EVs) are membrane‐enclosed particles that play an important role in cancer progression and have emerged as a promising source of circulating biomarkers. Protein S ‐acylation, frequently called palmitoylation, has been proposed as a post‐translational mechanism that modulates the dynamics of EV biogenesis and protein cargo sorting. However, technical challenges have limited large‐scale profiling of the whole palmitoyl‐proteins of EVs. We successfully employed a novel approach that combines low‐background acyl‐biotinyl exchange (LB‐ABE) with label‐free proteomics to analyse the palmitoyl‐proteome of large EVs (L‐EVs) and small EVs (S‐EVs) from prostate cancer cells. Here we report the first palmitoyl‐protein signature of EVs, and demonstrate that L‐ and S‐EVs harbour proteins associated with distinct biological processes and subcellular origin. We identified STEAP1, STEAP2, and ABCC4 as prostate cancer‐specific palmitoyl‐proteins abundant in both EV populations. Importantly, localization of the above proteins in EVs was reduced upon inhibition of palmitoylation in the producing cells. Our results suggest that this post‐translational modification may play a role in the sorting of the EV‐bound secretome and possibly enable selective detection of disease biomarkers.