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. 2023 Jul 10;13:11180. doi: 10.1038/s41598-023-38084-y

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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EVs biogenesis. Exosomes originate via the clathrin-mediated endocytic pathway. Cell membrane endocytosis results in the formation of early endosomes that develop late endosomes. Late endosomes’ membrane invaginates creating intraluminal vesicles (ILVs), originating multivesicular bodies (MVB). When MVB fuses with the plasma membrane, exosomes (originated from ILVs) are released. Conversly, ectosomes originate from direct budding from plasma membrane. Proteins with lipid anchors (garnet dots) accumulate and help curving the membrane as the bulge increases. Biomolecules accumulate within the bulges until they are cleaved and released as ectosomes. Spheresomes biogenesis begins via RER–Golgi-derived vesicles which aggregate beneath the cell membrane. As the number of vesicles increases, the cell membrane evaginates towards the extracellular space, originating a multivesicular sphere (MVS) that is subsequently released to the extracellular medium. MVS membrane rupture releases spherosomes. Membrane proteins (exosomes and ectosomes): pink and purples; RER-Golgi proteins (spheresomes): black and blue.