Related Experiment Video

Updated: Sep 15, 2025

Author Spotlight: Standardizing and Improving the Extraction and Purification of Extracellular Vesicles from Human ADSCs
04:54

Author Spotlight: Standardizing and Improving the Extraction and Purification of Extracellular Vesicles from Human ADSCs

Published on: May 3, 2024

837

ADAM Sheddase Activity Promotes the Detachment of Small Extracellular Vesicles From the Plasma Membrane

Chloé Bizingre1,2, Zaira Arellano-Anaya1,2, Flavien Picard3

  • 1INSERM UMR-S 1124, Paris, France.

Journal of Extracellular Vesicles
|July 17, 2025
PubMed

Insights

Small extracellular vesicles (SEVs) release is actively regulated by ADAM10/17 sheddases, which cleave adhesion proteins. This process is controlled by PDK1 and ERK1/2 signaling pathways, impacting SEV release in health and disease.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Small extracellular vesicles (SEVs) mediate intercellular communication in various physiological and pathological processes.
  • SEV release has been traditionally considered a passive event following the fusion of endocytic multivesicular bodies with the plasma membrane.

Purpose of the Study:

  • To investigate the molecular mechanisms regulating the release of small extracellular vesicles (SEVs).
  • To identify the role of specific proteases and signaling pathways in SEV detachment from the cell surface.

Main Methods:

  • Investigated the role of ADAM10 and ADAM17 sheddases in SEV release.
  • Analyzed the involvement of 3-phosphoinositide-dependent kinase 1 (PDK1), ERK1/2, and 90-kDa ribosomal S6 kinase-2 (RSK2) signaling pathways.
  • Examined the influence of iRhom2 on ADAM10/17 activity and SEV release.

Main Results:

  • ADAM10 and ADAM17 sheddases are crucial for the final detachment of SEVs from the cell surface by cleaving adhesion proteins.
  • SEV release intensity is modulated by the interplay between PDK1 and ERK1/2 signaling, converging on RSK2.
  • RSK2 regulates ADAM17 bioavailability and ADAM10/17 enzymatic activity, partly via iRhom2 levels.

Conclusions:

  • SEV release is an actively regulated proteolytic process, not merely passive.
  • Understanding ADAM10/17-mediated SEV discharge offers insights into pathological conditions involving SEV deregulation.
Keywords:
ERK1/2PDK1RSK2exosomesiRhom2protein cleavagesignalling

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