Protein Composition Reflects Extracellular Vesicle Heterogeneity

Abstract

Extracellular vesicles (EVs) are membrane‐enclosed particles that are released by virtually all cells from all living organisms. EVs shuttle biologically active cargo including protein, RNA, and DNA between cells. When shed by cancer cells, they function as potent intercellular messangers with important functional consequences. Cells produce a diverse spectrum of EVs, spanning from small vesicles of 40–150 nm in diameter, to large vesicles up to 10 μm in diameter. While this diversity was initially considered to be purely based on size, it is becoming evident that different classes of EVs, and different populations within one EV class may harbor distinct molecular cargo and play specific functions. Furthermore, there are considerable cell type‐dependent differences in the cargo and function of shed EVs. This review focuses on the most recent proteomic studies that have attempted to capture the EV heterogeneity by directly comparing the protein composition of different EV classes and EV populations derived from the same cell source. Recent studies comparing protein composition of the same EV class(es) derived from different cell types are also summarized. Emerging approaches to study EV heterogeneity and their important implications for future studies are also discussed.

Host- and Microbiota-Derived Extracellular Vesicles, Immune Function, and Disease Development

“…While different types of mechanisms have been proposed for exosome uptake, it is known that exosomes interact with the recipient cell, and transmit information resulting in changes in surrounding cells via (1) direct stimulation by membrane ligands; (2) receptor transfer between the donor cells and recipient cells; (3) transfer of genetic information; and (4) direct stimulation by endocytically-expressed surface receptors in recipient target cells [16]. Recently, a thorough description of their protein composition has led to an improved classification of EVs [17].…”

Deiminated proteins in extracellular vesicles and serum of llama (Lama glama)—Novel insights into camelid immunity

“…As PADs have been identified to be a key regulator of extracellular (EV)-release, a mechanism that has been found to be phylogenetically conserved from bacteria to mammals (Kholia et al, 2015;Kosgodage et al, 2017Kosgodage et al, , 2018Gavinho et al, 2019;Kosgodage et al, 2019), the characterisation of EVs in camelids is of further interest. Extracellular vesicles (EVs) are found in most body fluids and participate in cellular communication via transfer of cargo proteins and genetic material (Inal et al, 2013;Colombo et al, 2014;Lange et al, 2017;Turchinovich et al, 2019;Vagner et al, 2019). EVs in body fluids, including serum, can also be useful biomarkers to reflect health status (Hessvik and Llorente, 2018;Ramirez et al, 2018).…”

Tumor-derived extracellular vesicles: molecular parcels that enable regulation of the immune response in cancer

“…EVs possess a diverse collection of proteomic cargo (Greening et al, 2017;Vagner et al, 2019) that changes dynamically according to cell state and environmental conditions. For instance, Kreger et al (2016) found that transformation of mouse embryonic fibroblasts with an oncogenic form of diffuse B cell lymphoma (onco-Dbl) both increased the rate of microvesicle production, as well as altered their proteomic contents.…”