Mechanism of cargo sorting into small extracellular vesicles

Abstract

Extracellular vesicles (EVs) are special membranous structures released by almost every cell type that carry and protect some biomolecules from being degraded. They transport important signaling molecules involved in cell communication, migration, and numerous physiological processes. EVs can be categorized into two main types according to their size: i) small extracellular vesicles (sEVs), such as exosomes (30–150 nm), released from the fusion of multivesicular bodies (MVBs) with the plasma membrane, and ii) large EVs, such as microvesicles (100–1000 nm). These are no longer considered a waste product of cells, but regulators of intercellular communication, as they can transport specific repertoires of cargos, such as proteins, lipids, and nucleic acids to receptor cells to achieve cell-to-cell communication. This indicates the existence of different mechanisms, which controls the cargos sorting into EVs. This review mainly gives a description about the biological roles of the cargo and the sorting mechanisms of sEVs, especially exosomes.

Unconventional Protein Secretion Dependent on Two Extracellular Vesicles: Exosomes and Ectosomes

“…In addition to proteins, cargos contain molecules of different nature: various types of RNA (mostly microRNAs, miRs, together with messenger RNAs, mRNAs, long non-coding RNAs, lncRNAs, and ribosome RNAs, rRNAs), small sequences of DNA, lipids and metabolic molecules ( Figure 2A ) ( Yang and Gould, 2013 ; Ras-Carmona et al, 2021 ). Recent studies have shown ubiquitin and ubiquitin-like proteins to participate in protein post-translational modifications and in the control of protein complex composition ( Chen et al, 2021 ; Padovani et al, 2022 ), thus contributing to their accumulation within ILVs ( Yang and Gould, 2013 ; Chen et al, 2021 ; Ras-Carmona et al, 2021 ). Surface proteins of cargo are often anchored to the ILV membrane by myristoylation, palmitoylation or other sequences.…”

“…The mechanisms of cargo accumulation remain unclear. Discoveries of a few years ago demonstrated the targeting and association of single proteins to the growing ILV lumen ( Chen et al, 2021 ). Details have been clarified by the identification of proteins, such as endofin and arrestin-domain containing protein (ARRDC1), in the assembly of cargos ( Ageta and Tsuchida, 2019 ; Kazan et al, 2021 ).…”

“…Knowledge about ectosome cargo is limited. Accumulation of proteins by high affinity binding to miRNAs are processes known within exosomes ( Yang and Gould, 2013 ; Chen et al, 2021 ). They might occur also within the ectosome lumen.…”

Extracellular Vesicles: The Landscape in the Progression, Diagnosis, and Treatment of Triple-Negative Breast Cancer

“…Besides, miR-106a-5p packaged in MSC-derived exosomes promoted TNBC tumor progression in the xenograft, which could be suppressed by lncRNA HAND2-AS1. Tong Chen et al (2021) revealed that circHIF1A, which was upregulated in the plasma of BC patients, could be selectively loaded into exosomes secreted by BC cells. CircHIF1A promoted TNBC growth and metastasis by regulating NFIB expression and subcellular location and was involved in the circHIF1A/NFIB/FUS positive feedback loop.…”

“…Extracellular vesicles (EVs) are defined as membrane-bound vesicles released by various cell types under physiological and pathological conditions ( Clancy et al, 2015 ). Generally speaking, based on morphological features, EVs consist of three particles of different sizes in diameter, mainly including exosomes (30–150 nm), micro-vesicles (150–1,000 nm), and apoptotic bodies (500–2,000 nm) ( Yiwen Chen et al, 2021 ). EVs act as a reservoir that encloses a multitude of functional biomolecules, such as lipids, mRNAs, proteins, ncRNA, such as miRNA, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) ( Kondratov et al, 2020 ).…”