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Racchetti et al. Extracell Vesicles Circ Nucleic Acids 2023;4:44-58 https://dx.doi.org/10.20517/evcna.2023.03 Page 54

(assembled at the plasma membrane and then pinched off) have revealed mechanistically innovative vesicle
generation relevant to cellular physiology and pathology. Recently, two additional types of structures
(lysosomes and autophagosomes, already well known for their single intracellular functions) were
recognized to participate in vesicle generation. The entire process, therefore, is due to four types of
cytoplasmic structures characterized by distinct properties, interconnected by various functions, including
fusions, coordination with the exchange of molecules, and differential effects induced by their function.

Four distinct structures might appear too many to start governing vesicles and their EV generations with
subsequent intercellular communications. It should be considered, however, that these structures and their
products are substantially different. In most cells, MVBs and their exosomes predominate in numbers and
functions. Ectosomes (larger vesicles that is discharged faster) are the only ones directly assembled and
released from the plasma membrane. Endo-lysosome cargoes contain only a few vesicles with many
essential molecules and enzymes involved in extracellular protein turnover. Autophagosome function is
precisely regulated. With various structures and molecules, they release heterologous vesicles that remain to
be characterized in future analyses [40,90,103] . The properties of the four structures and their products have
opened the way to intercellular communications. In addition to their scientific progress, they have
substantial medical relevance, already presented by a vast body of literature.

DECLARATIONS
Authors contributions
The authors discussed the developments in the field and generated this presentation: Racchetti G
Wrote and revised the final version: Meldolesi J
All authors agreed to the final version.

Availability of data and materials
The data were obtained from PubMed, NCBI, USA, and our Institute’s and University’s libraries.

Financial support and sponsorship
Not applicable.

Conflicts of interest
Authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Obtained from the institutional ethics committee.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2023.

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