Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9

By Mathilde Mathieu, N. Névo, M. Jouve, J. I. Valenzuela, Mathieu Maurin, F. Verweij, Roberta Palmulli, D. Lankar, F. Dingli, D. Loew and 4 more. Nature Communications, 2021

722 citations recorded by the source corpus.

Despite their roles in intercellular communications, the different populations of extracellular vesicles (EVs) and their secretion mechanisms are not fully characterized: how and to what extent EVs form as intraluminal vesicles of endocytic compartments (exosomes), or at the plasma membrane (PM) (ectosomes) remains unclear. Here we follow intracellular trafficking of the EV markers CD9 and CD63 from the endoplasmic reticulum to their residency compartment, respectively PM and late endosomes. We observe transient co-localization at both places, before they finally segregate. CD9 and a mutant CD63 stabilized at the PM are more abundantly released in EVs than CD63. Thus, in HeLa cells, ectosomes are more prominent than exosomes. By comparative proteomic analysis and differential response to neutralization of endosomal pH, we identify a few surface proteins likely specific of either exosomes (LAMP1) or ectosomes (BSG, SLC3A2). Our work sets the path for molecular and functional discrimination of exosomes and small ectosomes in any cell type. Extracellular vesicles (EVs) play a role in intercellular communication, however the precise biogenesis of different populations of EVs are not clear. Here, the authors follow the intracellular trafficking of two proteins before their secretion in EVs and report the biogenesis and protein markers of EV subtypes: ectosomes budding from the plasma membrane as well as exosomes from late endosomes.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/dbacd623749f97068b616ffbc778cc7e56c32f0d

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Citations in the corpus

Challenges and directions in studying cell–cell communication by extracellular vesicles (2022, background): “The intracellular trafficking of the recruiting cargoes between plasma membrane and endosomes is also a major regulator of ectosome versus exosome biogenesis 15 , although still only modestly appreciated.”