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Detection of Exosomal Biomarker by Electric Field-induced Release and Measurement EFIRM
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Exosome Release Is Regulated by mTORC1.

Wenchong Zou1, Mingqiang Lai1, Yue Zhang1

  • 1Department of Cell Biology Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|February 19, 2019
PubMed
Summary

Mechanistic target of rapamycin complex 1 (mTORC1) negatively regulates exosome release. Inhibiting mTORC1 stimulates exosome release, similar to autophagy, impacting cellular communication.

Keywords:
MVBsTSC2exosomesmTORC1rapamycin

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Exosomes are nanovesicles involved in intercellular communication and waste management.
  • Exosome release involves cellular membrane and protein content loss.
  • Mechanistic target of rapamycin complex 1 (mTORC1) is a key regulator of cellular processes.

Purpose of the Study:

  • To investigate the role of mTORC1 in regulating exosome release.
  • To determine how mTORC1 inhibition affects exosome biogenesis and release.
  • To explore the relationship between mTORC1, autophagy, and exosome release.

Main Methods:

  • Cell culture and animal models were used.
  • mTORC1 activity was modulated using rapamycin and nutrient/growth factor deprivation.
  • Exosome release was quantified.
  • CD63-positive exosome precursors were analyzed.
  • Rab27A was downregulated using siRNA.
  • Exosomal cargo (protein and miRNA) was analyzed.

Main Results:

  • Sustained mTORC1 activation inhibits exosome release, causing accumulation of exosome precursors.
  • Inhibition of mTORC1 by rapamycin or nutrient deprivation stimulates exosome release.
  • Stimulated exosome release is dependent on the small GTPase Rab27A.
  • Inhibition of mTORC1 does not significantly alter the protein and miRNA cargo of released exosomes.
  • Exosome release occurs concomitantly with autophagy upon mTORC1 inhibition.

Conclusions:

  • Exosome release is negatively regulated by mTORC1, similar to autophagy.
  • mTORC1 acts as a signaling nexus controlling both autophagy and exosome release in response to nutrient and growth factor availability.
  • Rab27A is essential for the stimulated exosome release observed upon mTORC1 inhibition.