Extracellular vesicles (EVs) are lipid-enclosed structures that facilitate intercellular communication by transferring cargo between cells. Although predominantly studied in mammals, extracellular vesicles are ubiquitous across metazoans, and thus research in non-mammalian models is critical for fully elucidating extracellular vesicles biology. Recent advances demonstrate that extracellular vesicles mediate diverse physiological processes in non-mammalian vertebrates, including fish, amphibians, and reptiles. Piscine extracellular vesicles promote fin regeneration in zebrafish and carry heat shock proteins regulated by stress. Frog extracellular vesicles containing microRNAs modulate angiogenesis, while turtle extracellular vesicles coordinate reproductive functions. Venom from snakes contains extracellular vesicles that mirror the whole venom composition and interact with mammalian cells. Invertebrates also possess extracellular vesicles involved in immunity, development, and pathogenesis. Molluscan extracellular vesicles participate in shell formation and host interactions. Arthropod models, including Drosophila, genetically dissect conserved pathways controlling extracellular vesicles biogenesis and signalling. Nematode extracellular vesicles regulate larval development, animal communication, and ageing via conserved extracellular vesicles proteins. Ancient metazoan lineages utilise extracellular vesicles as well, with cnidarian extracellular vesicles regulating immunity and regeneration. Ultimately, expanding extracellular vesicles research beyond typical biomedical models to encompass phylogenetic diversity provides an unparalleled perspective on the conserved versus specialised aspects of metazoan extracellular vesicles roles over ∼500 million years. With a primary focus on the literature from the past 5 years, this review aims to reveal fundamental insights into EV-mediated intercellular communication mechanisms shaping animal physiology.

CENAB Faculty of Science Jan Evangelista Purkyně University Ústí nad Labem Czechia

Department of Biology Faculty of Science Jan Evangelista Purkyně University Ústí nad Labem Czechia

Zobrazit více v PubMed

Álvarez S., Contreras-Kallens P., Aguayo S., Ramírez O., Vallejos C., Ruiz J., et al. (2023). Royal jelly extracellular vesicles promote wound healing by modulating underlying cellular responses. Mol. Ther. Nucleic Acids 31, 541–552. 10.1016/j.omtn.2023.02.008 PubMed DOI PMC

Bai X., Guo Y., Shi Y., Lin J., Tarique I., Wang X., et al. (2019). In vivo multivesicular bodies and their exosomes in the absorptive cells of the zebrafish (Danio Rerio) gut. Fish. Shellfish Immunol. 88, 578–586. 10.1016/j.fsi.2019.03.030 PubMed DOI

Beer K. B., Wehman A. M. (2017). Mechanisms and functions of extracellular vesicle release in vivo-What we can learn from flies and worms. Cell Adh Migr. 11 (2), 135–150. 10.1080/19336918.2016.1236899 PubMed DOI PMC

Bowden T. J., Kraev I., Lange S. (2020a). Extracellular vesicles and post-translational protein deimination signatures in haemolymph of the American lobster (Homarus americanus). Fish. Shellfish Immunol. 106, 79–102. 10.1016/j.fsi.2020.06.053 PubMed DOI

Bowden T. J., Kraev I., Lange S. (2020b). Extracellular vesicles and post-translational protein deimination signatures in Mollusca-the blue mussel (Mytilus edulis), soft shell clam (mya arenaria), eastern oyster (Crassostrea virginica) and atlantic jacknife clam (Ensis leei). Biol. (Basel) 9 (12), 416. 10.3390/biology9120416 PubMed DOI PMC

Camelo C., Körte A., Jacobs T., Luschnig S. (2022). Tracheal tube fusion in Drosophila involves release of extracellular vesicles from multivesicular bodies. J. Cell Sci. 135 (3), jcs259590. 10.1242/jcs.259590 PubMed DOI

Carregari V. C., Rosa-Fernandes L., Baldasso P., Bydlowski S. P., Marangoni S., Larsen M. R., et al. (2018). Author correction: snake venom extracellular vesicles (SVEVs) reveal wide molecular and functional proteome diversity. Sci. Rep. 8 (1), 15908. 10.1038/s41598-018-33284-3 PubMed DOI PMC

Chen Q., Holt W. V. (2021). Extracellular vesicles in the male reproductive tract of the softshell turtle. Reprod. Fertil. Dev. 33, 519–529. 10.1071/RD20214 PubMed DOI

Chen X., Bai Z., Li J. (2019). The mantle exosome and MicroRNAs of hyriopsis cumingii involved in nacre color formation. Mar. Biotechnol. (NY) 21 (5), 634–642. 10.1007/s10126-019-09908-8 PubMed DOI

Criscitiello M. F., Kraev I., Lange S. (2019). Deiminated proteins in extracellular vesicles and plasma of nurse shark (Ginglymostoma cirratum) - novel insights into shark immunity. Fish. Shellfish Immunol. 92, 249–255. 10.1016/j.fsi.2019.06.012 PubMed DOI

Criscitiello M. F., Kraev I., Petersen L. H., Lange S. (2020). Deimination protein profiles in Alligator mississippiensis reveal plasma and extracellular vesicle-specific signatures relating to immunity, metabolic function, and gene regulation. Front. Immunol. 11, 651. 10.3389/fimmu.2020.00651 PubMed DOI PMC

D'Alessio S., Buckley K. M., Kraev I., Hayes P., Lange S. (2021). Extracellular vesicle signatures and post-translational protein deimination in purple sea urchin (Strongylocentrotus purpuratus) coelomic fluid-novel insights into echinodermata biology. Biol. (Basel) 10 (9), 866. 10.3390/biology10090866 PubMed DOI PMC

Danilchik M., Tumarkin T. (2017). Exosomal trafficking in Xenopus development. Genesis 55 (1-2), e23011. 10.1002/dvg.23011 PubMed DOI

Faught E., Henrickson L., Vijayan M. M. (2017). Plasma exosomes are enriched in Hsp70 and modulated by stress and cortisol in rainbow trout. J. Endocrinol. 232 (2), 237–246. 10.1530/JOE-16-0427 PubMed DOI

Fratantonio D., Munir J., Shu J., Howard K., Baier S. R., Cui J., et al. (2023). The RNA cargo in small extracellular vesicles from chicken eggs is bioactive in C57BL/6 J mice and human peripheral blood mononuclear cells ex vivo . Front. Nutr. 10, 1162679. 10.3389/fnut.2023.1162679 PubMed DOI PMC

Gonçalves-Machado L., Verçoza B. R. F., Nogueira F. C. S., Melani R. D., Domont G. B., Rodrigues S. P., et al. (2022). Extracellular vesicles from Bothrops jararaca venom are diverse in structure and protein composition and interact with mammalian cells. Toxins 14 (11), 806. 10.3390/toxins14110806 PubMed DOI PMC

Gross J. C., Chaudhary V., Bartscherer K., Boutros M. (2012). Active Wnt proteins are secreted on exosomes. Nat. Cell Biol. 14 (10), 1036–1045. 10.1038/ncb2574 PubMed DOI

Guatelli S., Ferrario C., Bonasoro F., Anjo S. I., Manadas B., Candia Carnevali M. D., et al. (2022). More than a simple epithelial layer: multifunctional role of echinoderm coelomic epithelium. Cell Tissue Res. 390 (2), 207–227. 10.1007/s00441-022-03678-x PubMed DOI PMC

Harding C., Heuser J., Stahl P. (1983). Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J. Cell Biol. 97 (2), 329–339. 10.1083/jcb.97.2.329 PubMed DOI PMC

Janouskova O., Herma R., Semeradtova A., Poustka D., Liegertova M., Hana Auer M., et al. (2022). Conventional and nonconventional sources of exosomes-isolation methods and influence on their downstream biomedical application. Front. Mol. Biosci. 9, 846650. 10.3389/fmolb.2022.846650 PubMed DOI PMC

Jayathilaka E., Edirisinghe S. L., Lee J., Nikapitiya C., De Zoysa M. (2022). Isolation and characterization of plasma-derived exosomes from olive flounder (Paralichthys olivaceus) and their wound healing and regeneration activities. Fish. Shellfish Immunol. 128, 196–205. 10.1016/j.fsi.2022.07.076 PubMed DOI

Kobayashi-Sun J., Yamamori S., Kondo M., Kuroda J., Ikegame M., Suzuki N., et al. (2020). Uptake of osteoblast-derived extracellular vesicles promotes the differentiation of osteoclasts in the zebrafish scale. Commun. Biol. 3 (1), 190. 10.1038/s42003-020-0925-1 PubMed DOI PMC

Lefebvre F. A., Benoit Bouvrette L. P., Perras L., Blanchet-Cohen A., Garnier D., Rak J., et al. (2016). Comparative transcriptomic analysis of human and Drosophila extracellular vesicles. Sci. Rep. 6, 27680. 10.1038/srep27680 PubMed DOI PMC

Liégeois S., Benedetto A., Garnier J. M., Schwab Y., Labouesse M. (2006). The V0-ATPase mediates apical secretion of exosomes containing Hedgehog-related proteins in Caenorhabditis elegans. J. Cell Biol. 173 (6), 949–961. 10.1083/jcb.200511072 PubMed DOI PMC

Liegertová M., Semerádtová A., Kocholatá M., Průšová M., Němcová L., Štofik M., et al. (2022). Mucus-derived exosome-like vesicles from the Spanish slug (arion vulgaris): taking advantage of invasive pest species in biotechnology. Sci. Rep. 12 (1), 21768. 10.1038/s41598-022-26335-3 PubMed DOI PMC

Luo X., Guo Y., Huang Y., Cheng M., Wu X., Gong Y. (2022). Characterization and proteomics of chicken seminal plasma extracellular vesicles. Reprod. Domest. Anim. 57 (1), 98–110. 10.1111/rda.14033 PubMed DOI

Ma J., Wang Y. T., Chen L. H., Yang B. Y., Jiang Y. Z., Wang L. X., et al. (2023). Dauer larva-derived extracellular vesicles extend the life of Caenorhabditis elegans. Biogerontology 24 (4), 581–592. 10.1007/s10522-023-10030-5 PubMed DOI PMC

Magnadóttir B., Kraev I., Dodds A. W., Lange S. (2021). The proteome and citrullinome of Hippoglossus hippoglossus extracellular vesicles-novel insights into roles of the serum secretome in immune, gene regulatory and metabolic pathways. Int. J. Mol. Sci. 22 (2), 875. 10.3390/ijms22020875 PubMed DOI PMC

Manuwar A., Dreyer B., Böhmert A., Ullah A., Mughal Z., Akrem A., et al. (2020). Proteomic investigations of two Pakistani Naja snake venoms species unravel the venom complexity, posttranslational modifications, and presence of extracellular vesicles. Toxins (Basel) 12 (11), 669. 10.3390/toxins12110669 PubMed DOI PMC

Moros M., Fergola E., Marchesano V., Mutarelli M., Tommasini G., Miedziak B., et al. (2021). The aquatic invertebrate Hydra vulgaris releases molecular messages through extracellular vesicles. Front. Cell Dev. Biol. 9, 788117. 10.3389/fcell.2021.788117 PubMed DOI PMC

Muñoz E. L., Fuentes F. B., Felmer R. N., Yeste M., Arias M. E. (2022). Extracellular vesicles in mammalian reproduction: A review. Zygote 30 (4), 440–463. 10.1017/S0967199422000090 PubMed DOI

Ogawa Y., Kanai-Azuma M., Akimoto Y., Kawakami H., Yanoshita R. (2008). Exosome-like vesicles in Gloydius blomhoffii blomhoffii venom. Toxicon 51 (6), 984–993. 10.1016/j.toxicon.2008.02.003 PubMed DOI

Oliva Chávez A. S., Wang X., Marnin L., Archer N. K., Hammond H. L., Carroll E. E. M., et al. (2021). Tick extracellular vesicles enable arthropod feeding and promote distinct outcomes of bacterial infection. Nat. Commun. 12 (1), 3696. 10.1038/s41467-021-23900-8 PubMed DOI PMC

Peršurić Z., Pavelić S. K. (2021). Bioactives from bee products and accompanying extracellular vesicles as novel bioactive components for wound healing. Molecules 26 (12), 3770. 10.3390/molecules26123770 PubMed DOI PMC

Rast J. P., D'Alessio S., Kraev I., Lange S. (2021). Post-translational protein deimination signatures in sea lamprey (Petromyzon marinus) plasma and plasma-extracellular vesicles. Dev. Comp. Immunol. 125, 104225. 10.1016/j.dci.2021.104225 PubMed DOI

Russell J. C., Kim T. K., Noori A., Merrihew G. E., Robbins J. E., Golubeva A., et al. (2020). Composition of Caenorhabditis elegans extracellular vesicles suggests roles in metabolism, immunity, and aging. Geroscience 42 (4), 1133–1145. 10.1007/s11357-020-00204-1 PubMed DOI PMC

Sanchez-Lopez J. A., Twena S., Apel I., Kornhaeuser S. C., Chasnitsky M., Miklosi A. G., et al. (2022). Male-female communication enhances release of extracellular vesicles leading to high fertility in Drosophila. Commun. Biol. 5 (1), 815. 10.1038/s42003-022-03770-6 PubMed DOI PMC

Schuh C., Aguayo S., Zavala G., Khoury M. (2019). Exosome-like vesicles in Apis mellifera bee pollen, honey and royal jelly contribute to their antibacterial and pro-regenerative activity. J. Exp. Biol. 222 (20), jeb208702. 10.1242/jeb.208702 PubMed DOI

Scott A., Sueiro Ballesteros L., Bradshaw M., Tsuji C., Power A., Lorriman J., et al. (2021). In vivo characterization of endogenous cardiovascular extracellular vesicles in larval and adult zebrafish. Arterioscler. Thromb. Vasc. Biol. 41 (9), 2454–2468. 10.1161/ATVBAHA.121.316539 PubMed DOI PMC

Sugimoto K., Toume K. (2021). Amphibian thrombocyte-derived extracellular vesicles, including microRNAs, induce angiogenesis-related genes in endothelial cells. Genes cells. 26 (10), 757–771. 10.1111/gtc.12882 PubMed DOI

Takagi T., Yoshioka Y., Zayasu Y., Satoh N., Shinzato C. (2020). Transcriptome analyses of immune system behaviors in primary polyp of coral acropora digitifera exposed to the bacterial pathogen Vibrio coralliilyticus under thermal loading. Mar. Biotechnol. (NY) 22 (6), 748–759. 10.1007/s10126-020-09984-1 PubMed DOI

van Niel G., D'Angelo G., Raposo G. (2018). Shedding light on the cell biology of extracellular vesicles. Nat. Rev. Mol. Cell Biol. 19 (4), 213–228. 10.1038/nrm.2017.125 PubMed DOI

Verweij F. J., Hyenne V., Van Niel G., Goetz J. G. (2019). Extracellular vesicles: catching the light in zebrafish. Trends Cell Biol. 29 (10), 770–776. 10.1016/j.tcb.2019.07.007 PubMed DOI

Wang J., Barr M. M. (2016). Ciliary extracellular vesicles: txt msg organelles. Cell Mol. Neurobiol. 36 (3), 449–457. 10.1007/s10571-016-0345-4 PubMed DOI PMC

Wang Q.-Q., Lan X.-Q., Wei X.-S., Xu S.-M., Liu L.-Z., Bian X.-L., et al. (2023). Amphibian pore-forming protein βγ-CAT drives metabolite release from small extracellular vesicles through channel formation. Zoological Res. 44 (4), 739–742. 10.24272/j.issn.2095-8137.2022.510 PubMed DOI PMC

Wei X. S., Liu L. Z., Bian X. L., Zeng L., Lee W. H., Lin L., et al. (2022). Protein composition of extracellular vesicles from skin secretions of the amphibian Bombina maxima. Zool. Res. 43 (4), 687–690. 10.24272/j.issn.2095-8137.2022.069 PubMed DOI PMC

Willard N. K., Salazar E., Oyervides F. A., Wiebe C. S., Ocheltree J. S., Cortez M., et al. (2021). Proteomic identification and quantification of snake venom biomarkers in venom and plasma extracellular vesicles. Toxins (Basel) 13 (9), 654. 10.3390/toxins13090654 PubMed DOI PMC

Xu B., Zhang Y., Du X. F., Li J., Zi H. X., Bu J. W., et al. (2017). Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity. Cell Res. 27 (7), 882–897. 10.1038/cr.2017.62 PubMed DOI PMC

Xun C., Wang L., Yang H., Xiao Z., Deng M., Xu R., et al. (2021). Origin and characterization of extracellular vesicles present in the spider venom of Ornithoctonus hainana. Toxins (Basel) 13 (8), 579. 10.3390/toxins13080579 PubMed DOI PMC

Zhou W., Woodson M., Neupane B., Bai F., Sherman M. B., Choi K. H., et al. (2018). Exosomes serve as novel modes of tick-borne flavivirus transmission from arthropod to human cells and facilitates dissemination of viral RNA and proteins to the vertebrate neuronal cells. PLoS Pathog. 14 (1), e1006764. 10.1371/journal.ppat.1006764 PubMed DOI PMC

Zhu X., Wang S., Tarique I., An T., Yang H., Bai X., et al. (2019). Cellular evidence and source of exosomes in the biliary system of the Chinese soft-shelled turtle, pelodiscus sinensis. Front. Physiol. 10, 1097. 10.3389/fphys.2019.01097 PubMed DOI PMC