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Racchetti et al. Extracell Vesicles Circ Nucleic Acids 2023;4:44-58 Extracellular Vesicles and
DOI: 10.20517/evcna.2023.03
Circulating Nucleic Acids

Review Open Access

Four distinct cytoplasmic structures generate and
release specific vesicles, thus opening the way to

intercellular communication

1
Gabriella Racchetti , Jacopo Meldolesi 1,2
1
San Raffaele Institute, Vita-Salute San Raffaele University, Milan 20132, Italy.
2
CNR Institute of Neuroscience at the Milano-Bicocca University, Vedano al Lambro, Milan 20854, Italy.
Correspondence to: Jacopo Meldolesi, Emeritus Professor, San Raffaele Institute, Vita-Salute San Raffaele University, 58 via
Olgettina, Milan 20132, Italy. E-mail: meldolesi.jacopo@hsr.it

How to cite this article: Racchetti G, Meldolesi J. Four distinct cytoplasmic structures generate and release specific vesicles, thus
opening the way to intercellular communication. Extracell Vesicles Circ Nucleic Acids 2023;4:44-58.
https://dx.doi.org/10.20517/evcna.2023.03
Received: 11 Jan 2023 First Decision: 16 Feb 2023 Revised: 28 Feb 2023 Accepted: 7 Mar 2023 Published: 15 Mar 2023

Academic Editor: Yoke Peng Loh Copy Editor: Ying Han Production Editor: Ying Han

Abstract
In all cells, generation and release of specific vesicles are the initial steps of back-and-forth intercellular
communication. These processes are critical in normal physiology and pathophysiology. Vesicles have particular
functions appropriate to their targets. When stimulated, they are released into the extracellular space. Four
cytoplasmic membrane-bound structures generate their particular vesicles. Among these structures, multivesicular
bodies (MVBs) can accumulate many small vesicles in their lumen; release occurs upon MVB exocytosis.
Ectosomes are larger vesicles characterized by their responses and are generated directly and released
independently from specific microdomains pre-established in the thickness of the plasma membrane. Most
lysosomes do not generate vesicles. However, unique components of a minor form, the endo-lysosome, constitute
the third class of structures that release a few vesicles by exocytosis with molecules and structures inducing
changes in the extracellular environment. The autophagosome, the fourth structure, releases several
heterogeneous vesicles by exocytosis with malformed bio-molecules, assembled structures, and damaged
organelles. Interestingly, the frequent interaction of autophagosomes with MVBs and their exosomes contributes
to the regulation and intensity of their action. The specificity and function of released vesicles depend on their
membranes’ and luminal cargoes’ composition and dynamics. An ongoing investigation of the various vesicles
reveals new properties regarding their generation, release, and resulting extracellular processes. The growth of
information about structures and their vesicles progressively extends the knowledge base regarding cell

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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