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The Machinery of Exosomes: Biogenesis, Release, and Uptake

Krylova, Sofia V., Feng, Daorong·2023·International Journal of Molecular Sciences

Abstract

Exosomes are a subtype of membrane-contained vesicles 40–200 nm in diameter that are secreted by cells into their surroundings. By transporting proteins, lipids, mRNA, miRNA, lncRNA, and DNA, exosomes are able to perform such vital functions as maintaining cellular homeostasis, removing cellular debris, and facilitating intercellular and interorgan communication. Exosomes travel in all body fluids and deliver their molecular messages in autocrine, paracrine as well as endocrine manners. In recent years, there has been an increased interest in studying exosomes as diagnostic markers and therapeutic targets, since in many disease conditions this machinery becomes dysregulated or hijacked by pathological processes. Additionally, delivery of exosomes and exosomal miRNA has already been shown to improve systemic metabolism and inhibit progression of cancer development in mice. However, the subcellular machinery of exosomes, including their biogenesis, release and uptake, remains largely unknown. This review will bring molecular details of these processes up to date with the goal of expanding the knowledge basis for designing impactful exosome experiments in the future.

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Figure 1 Schematic of the exosome machinery. Cargos are sorted by endocytosis to the early endosomes. Early endosomes are committed to the endosomal maturation pathway, which results in multivesicular appearance of the late endosomes (MVB). Finally, MVBs fuse with the plasma membrane (PM) to release exosomes. Created with BioRender.com.
Figure 1 Schematic of the exosome machinery. Cargos are sorted by endocytosis to the early endosomes. Early endosomes are committed to the endosomal maturation pathway, which results in multivesicular appearance of the late endosomes (MVB). Finally, MVBs fuse with the plasma membrane (PM) to release exosomes. Created with BioRender.com.CC BY · PubMed Central
Figure 2 Exosome biogenesis. (A) ESCRT-dependent ILVs biogenesis. 1. Classic pathways from ESCRT 0-III-Vps4. 2. ESCRT 0-Bro1/ALIX-ESCRT III. 3. ALIX-ESCRT III. 4. Bro1-Vps4-ESCRT III. (B) ESCRT-independent ILVs biogenesis. Created with BioRender.com.
Figure 2 Exosome biogenesis. (A) ESCRT-dependent ILVs biogenesis. 1. Classic pathways from ESCRT 0-III-Vps4. 2. ESCRT 0-Bro1/ALIX-ESCRT III. 3. ALIX-ESCRT III. 4. Bro1-Vps4-ESCRT III. (B) ESCRT-independent ILVs biogenesis. Created with BioRender.com.CC BY · PubMed Central
Figure 3 Cargo sorting into exosomes. The known pathways of protein, RNA, and DNA sorting are depicted. Exosomal membrane proteins including tetraspanins, flotillin, integrins, MHCs, and ESCRT are labeled. Created with BioRender.com.
Figure 3 Cargo sorting into exosomes. The known pathways of protein, RNA, and DNA sorting are depicted. Exosomal membrane proteins including tetraspanins, flotillin, integrins, MHCs, and ESCRT are labeled. Created with BioRender.com.CC BY · PubMed Central
Figure 4 Exosome secretion. With the help of microtubules, Rabs, and tethering factors, one vesicle SNARE (V-SNARE) forms four-helix bundles with two target SNAREs (T-SNARE) to drive the fusion between MVB with plasma membranes to secret exosomes. Created with BioRender.com.
Figure 4 Exosome secretion. With the help of microtubules, Rabs, and tethering factors, one vesicle SNARE (V-SNARE) forms four-helix bundles with two target SNAREs (T-SNARE) to drive the fusion between MVB with plasma membranes to secret exosomes. Created with BioRender.com.CC BY · PubMed Central
Figure 5 Exosome uptake. Exosome uptake occurs via one of three pathways: (1) Fusion with the plasma membrane to release exosome contents; (2) Endocytosis; (3) Direct interaction with surface receptors. Created with BioRender.com.
Figure 5 Exosome uptake. Exosome uptake occurs via one of three pathways: (1) Fusion with the plasma membrane to release exosome contents; (2) Endocytosis; (3) Direct interaction with surface receptors. Created with BioRender.com.CC BY · PubMed Central

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Metadata

Authors
Krylova, S. V., & Feng, D.
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2023-01-10
Volume
24
Issue
2
Pages
1337
ISSN
1422-0067
Cited by
678
References
9
Language
en

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