Exosome biogenesis, secretion, and uptake edit
Exosomes biogenesis edit
Exosome formation starts with the invagination of the the multi-vesicular bodies (MVBs) or late endosomes to generate intraluminal vesicles (ILVs)[1]. There are various proposed mechanisms for formation of MVBs, vesicle budding, and sorting. The most studies and well known is the endosomal sorting complex required for transport (ESCRT )dependent pathway. ESCRT machinery mediates the ubiquitinated pathway consisting of protein complexes; ESCRT-0, -I, -II, -III, and the associated ATPase Vps4. ESCRT 0 recognizes and retains ubiquitinated proteins marked for packaging in the late endosomal membrane. ESCRT I/II recognizes the ESCRT 0 and starts creating involution of the membrane into the MVB. ESCRTIII forms a spiral shaped structure constricting the neck. ATPase VPS4 protein drives the membrane scission[2]. Syndecan-syntenin-ALIX exosome biogenesis pathway are one of the ESCRT-independent or non-canonical pathways for exosome biogenesis[3].
Exosome secretion edit
The MVBs once formed are trafficked to the internal side of the plasma membrane. These MVBs are transported to the plasma membrane leading to fusion[4]. Many studies have shown that MVBs having higher cholesterol content fuse with the plasma membrane thus releasing exosomes[5].The Rab proteins especially Rab 7 attached to the MVB recognizes its effector receptor. The SNARE complex (soluble N- ethylmaleimide- sensitive fusion attachment protein receptor) from the MVB and the plasma membrane interacts and mediates fusion.
Exosome uptake edit
One of the most prime interest in exosome research is due to the specificity of targeting by exosomes. The exact mechanisms is yet limited with docking of the exosomes with specific protein, sugar, or lipid interactions, or through micro (or micropinocytosis). The internalized exosomes are targeted to the endosomes which release their content in the recipient cell[6]
Sorting and packaging of cargoes in exosomes edit
Exosomes contain different cargoes; proteins, lipids, and nucleic acids. These cargoes are specifically sorted and packaged into exosomes. The contents packaged into exosomes are cell type specific and also influenced by cellular conditions[7]. Exosomal microRNAs (exomiRs) and proteins are sorted and packaged in exosomes. Villarroya-Beltri and colleagues identified a conserved GGAG specific motif, EXOmotif, in the miRNA packaged in the exosomes which was absent in the cytosolic miRNA (CLmiRNA), which binds to sumoylated heterogeneous nuclear riboprotein (hnRNP) A2B1 for exosome specific miRNA packaging[8]. Proteins are packaged in ESCRT, tertraspanins, lipid- dependent mechanisms[9]. Exosomes are enriched in cholesterol, spingomyelin, saturated phosphatidylcholine and phosphatyletanolamine as compared to the plasma membrane of the cell[10].
- ^ Hessvik, Nina Pettersen; Llorente, Alicia (2018-01). "Current knowledge on exosome biogenesis and release". Cellular and Molecular Life Sciences. 75 (2): 193–208. doi:10.1007/s00018-017-2595-9. ISSN 1420-682X. PMC 5756260. PMID 28733901.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) - ^ Wollert, Thomas; Hurley, James H. (2010-4). "Molecular mechanism of multivesicular body biogenesis by ESCRT complexes". Nature. 464 (7290): 864–869. doi:10.1038/nature08849. ISSN 0028-0836. PMC 2851844. PMID 20305637.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) - ^ Baietti, Maria Francesca; Zhang, Zhe; Mortier, Eva; Melchior, Aurélie; Degeest, Gisèle; Geeraerts, Annelies; Ivarsson, Ylva; Depoortere, Fabienne; Coomans, Christien; Vermeiren, Elke; Zimmermann, Pascale (2012-7). "Syndecan–syntenin–ALIX regulates the biogenesis of exosomes". Nature Cell Biology. 14 (7): 677–685. doi:10.1038/ncb2502. ISSN 1465-7392.
{{cite journal}}: Check date values in:|date=(help) - ^ Hessvik, Nina Pettersen; Llorente, Alicia (2018-01). "Current knowledge on exosome biogenesis and release". Cellular and Molecular Life Sciences. 75 (2): 193–208. doi:10.1007/s00018-017-2595-9. ISSN 1420-682X. PMC 5756260. PMID 28733901.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) - ^ Möbius, Wiebke; Ohno-Iwashita, Yoshiko; Donselaar, Elly G. van; Oorschot, Viola M.J.; Shimada, Yukiko; Fujimoto, Toyoshi; Heijnen, Harry F.G.; Geuze, Hans J.; Slot, Jan W. (2002-01). "Immunoelectron Microscopic Localization of Cholesterol Using Biotinylated and Non-cytolytic Perfringolysin O". Journal of Histochemistry & Cytochemistry. 50 (1): 43–55. doi:10.1177/002215540205000105. ISSN 0022-1554.
{{cite journal}}: Check date values in:|date=(help) - ^ Mathieu, Mathilde; Martin-Jaular, Lorena; Lavieu, Grégory; Théry, Clotilde (2019-1). "Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication". Nature Cell Biology. 21 (1): 9–17. doi:10.1038/s41556-018-0250-9. ISSN 1465-7392.
{{cite journal}}: Check date values in:|date=(help) - ^ Hessvik, Nina Pettersen; Llorente, Alicia (2018-01). "Current knowledge on exosome biogenesis and release". Cellular and Molecular Life Sciences. 75 (2): 193–208. doi:10.1007/s00018-017-2595-9. ISSN 1420-682X. PMC 5756260. PMID 28733901.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) - ^ Villarroya-Beltri, Carolina; Gutiérrez-Vázquez, Cristina; Sánchez-Cabo, Fátima; Pérez-Hernández, Daniel; Vázquez, Jesús; Martin-Cofreces, Noa; Martinez-Herrera, Dannys Jorge; Pascual-Montano, Alberto; Mittelbrunn, María; Sánchez-Madrid, Francisco (2013-12). "Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs". Nature Communications. 4 (1): 2980. doi:10.1038/ncomms3980. ISSN 2041-1723. PMC 3905700. PMID 24356509.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) - ^ Villarroya-Beltri, Carolina; Baixauli, Francesc; Gutiérrez-Vázquez, Cristina; Sánchez-Madrid, Francisco; Mittelbrunn, María (2014-10). "Sorting it out: Regulation of exosome loading". Seminars in Cancer Biology. 28: 3–13. doi:10.1016/j.semcancer.2014.04.009. PMC 4640178. PMID 24769058.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) - ^ Villarroya-Beltri, Carolina; Baixauli, Francesc; Gutiérrez-Vázquez, Cristina; Sánchez-Madrid, Francisco; Mittelbrunn, María (2014-10). "Sorting it out: Regulation of exosome loading". Seminars in Cancer Biology. 28: 3–13. doi:10.1016/j.semcancer.2014.04.009. PMC 4640178. PMID 24769058.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link)