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Extracellular vesicles, including large translating vesicles called midbody remnants, are released during the cell cycle.

Authors :
Patel SA
Park S
Zhu D
Torr EE
Dureke AG
McIntyre A
Muzyka N
Severson J
Skop AR
Source :
Molecular biology of the cell [Mol Biol Cell] 2024 Dec 01; Vol. 35 (12), pp. ar155. Date of Electronic Publication: 2024 Nov 13.
Publication Year :
2024

Abstract

Extracellular vesicles (EVs) play crucial roles in cell-cell communication, but the biogenesis of large EVs has remained elusive. Here, we show that the biogenesis of large EVs (>800 nm-2 µm) occurs predominantly through the completion of successful cytokinesis, and the majority of large EVs are midbody remnants (MBRs) with translation activity, and the unique marker MKLP1. Blocking the cell cycle or cytokinesis, genetically or chemically, significantly decreases MBRs and large (800 nm-2 µm), medium (500-800 nm), and small (<300 nm) EVs, suggesting that proliferative cells can also generate all sizes of EVs. The canonical EV markers including CD9, CD63, CD81 localize to the spindle midzone, midbody, and MBRs, suggesting that these markers are not specific for detecting EVs exclusively. Importantly, all commonly used EV isolation methods isolate MBRs, confounding previous EV research. Last, isolated MBRs maintain translation activity regardless of the isolation method. We propose a model for the biogenesis of EVs throughout the cell cycle and suggest that some large EVs are primarily generated from mitotic cells. The discovery of MBRs as a unique class of large, translating EVs has implications for using them as cancer diagnostic markers and for engineering them for therapeutic cargo delivery during mitosis.

Details

Language :
English
ISSN :
1939-4586
Volume :
35
Issue :
12
Database :
MEDLINE
Journal :
Molecular biology of the cell
Publication Type :
Academic Journal
Accession number :
39535882
Full Text :
https://doi.org/10.1091/mbc.E23-10-0384