Exosome Release Is Regulated by mTORC1

Wenchong Zou, Mingqiang Lai, Yue Zhang, Lei Zheng, Zhe Xing, Ting Li, Zhipeng Zou, Qiancheng Song, Xiaoyang Zhao, Laixin Xia, Jian Yang, Anling Liu, Han Zhang, Zhong Kai Cui, Yu Jiang, Xiaochun Bai

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Exosomes are small membrane-bound vesicles released into extracellular spaces by many types of cells. These nanovesicles carry proteins, mRNA, and miRNA, and are involved in cell waste management and intercellular communication. In the present study, it is shown that exosome release, which leads to net loss of cellular membrane and protein content, is negatively regulated by mechanistic target of rapamycin complex 1 (mTORC1). It is found that in cells and animal models exosome release is inhibited by sustained activation of mTORC1, leading to intracellular accumulation of CD63-positive exosome precursors. Inhibition of mTORC1 by rapamycin or nutrient and growth factor deprivation stimulates exosome release, which occurs concomitantly with autophagy. The drug-stimulated release is blocked by siRNA-mediated downregulation of small GTPase Rab27A. Analysis of the cargo content in exosomes released from rapamycin-treated cells reveals that inhibition of mTORC1 does not significantly alter its majority protein and miRNA profiles. These observations demonstrate that exosome release, like autophagy, is negatively regulated by mTORC1 in response to changes in nutrient and growth factor conditions.

Original languageEnglish (US)
Article number1801313
JournalAdvanced Science
Volume6
Issue number3
DOIs
StatePublished - Feb 6 2019

Fingerprint

Exosomes
Proteins
Nutrients
Membranes
nutrients
Sirolimus
proteins
cells
MicroRNAs
Waste management
Intercellular Signaling Peptides and Proteins
Autophagy
deprivation
waste management
membranes
Animals
Chemical activation
Cells
animal models
cargo

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Zou, W., Lai, M., Zhang, Y., Zheng, L., Xing, Z., Li, T., ... Bai, X. (2019). Exosome Release Is Regulated by mTORC1. Advanced Science, 6(3), [1801313]. https://doi.org/10.1002/advs.201801313
Zou, Wenchong ; Lai, Mingqiang ; Zhang, Yue ; Zheng, Lei ; Xing, Zhe ; Li, Ting ; Zou, Zhipeng ; Song, Qiancheng ; Zhao, Xiaoyang ; Xia, Laixin ; Yang, Jian ; Liu, Anling ; Zhang, Han ; Cui, Zhong Kai ; Jiang, Yu ; Bai, Xiaochun. / Exosome Release Is Regulated by mTORC1. In: Advanced Science. 2019 ; Vol. 6, No. 3.
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Zou, W, Lai, M, Zhang, Y, Zheng, L, Xing, Z, Li, T, Zou, Z, Song, Q, Zhao, X, Xia, L, Yang, J, Liu, A, Zhang, H, Cui, ZK, Jiang, Y & Bai, X 2019, 'Exosome Release Is Regulated by mTORC1', Advanced Science, vol. 6, no. 3, 1801313. https://doi.org/10.1002/advs.201801313

Exosome Release Is Regulated by mTORC1. / Zou, Wenchong; Lai, Mingqiang; Zhang, Yue; Zheng, Lei; Xing, Zhe; Li, Ting; Zou, Zhipeng; Song, Qiancheng; Zhao, Xiaoyang; Xia, Laixin; Yang, Jian; Liu, Anling; Zhang, Han; Cui, Zhong Kai; Jiang, Yu; Bai, Xiaochun.

In: Advanced Science, Vol. 6, No. 3, 1801313, 06.02.2019.

Research output: Contribution to journalArticle

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AU - Zou, Wenchong

AU - Lai, Mingqiang

AU - Zhang, Yue

AU - Zheng, Lei

AU - Xing, Zhe

AU - Li, Ting

AU - Zou, Zhipeng

AU - Song, Qiancheng

AU - Zhao, Xiaoyang

AU - Xia, Laixin

AU - Yang, Jian

AU - Liu, Anling

AU - Zhang, Han

AU - Cui, Zhong Kai

AU - Jiang, Yu

AU - Bai, Xiaochun

PY - 2019/2/6

Y1 - 2019/2/6

N2 - Exosomes are small membrane-bound vesicles released into extracellular spaces by many types of cells. These nanovesicles carry proteins, mRNA, and miRNA, and are involved in cell waste management and intercellular communication. In the present study, it is shown that exosome release, which leads to net loss of cellular membrane and protein content, is negatively regulated by mechanistic target of rapamycin complex 1 (mTORC1). It is found that in cells and animal models exosome release is inhibited by sustained activation of mTORC1, leading to intracellular accumulation of CD63-positive exosome precursors. Inhibition of mTORC1 by rapamycin or nutrient and growth factor deprivation stimulates exosome release, which occurs concomitantly with autophagy. The drug-stimulated release is blocked by siRNA-mediated downregulation of small GTPase Rab27A. Analysis of the cargo content in exosomes released from rapamycin-treated cells reveals that inhibition of mTORC1 does not significantly alter its majority protein and miRNA profiles. These observations demonstrate that exosome release, like autophagy, is negatively regulated by mTORC1 in response to changes in nutrient and growth factor conditions.

AB - Exosomes are small membrane-bound vesicles released into extracellular spaces by many types of cells. These nanovesicles carry proteins, mRNA, and miRNA, and are involved in cell waste management and intercellular communication. In the present study, it is shown that exosome release, which leads to net loss of cellular membrane and protein content, is negatively regulated by mechanistic target of rapamycin complex 1 (mTORC1). It is found that in cells and animal models exosome release is inhibited by sustained activation of mTORC1, leading to intracellular accumulation of CD63-positive exosome precursors. Inhibition of mTORC1 by rapamycin or nutrient and growth factor deprivation stimulates exosome release, which occurs concomitantly with autophagy. The drug-stimulated release is blocked by siRNA-mediated downregulation of small GTPase Rab27A. Analysis of the cargo content in exosomes released from rapamycin-treated cells reveals that inhibition of mTORC1 does not significantly alter its majority protein and miRNA profiles. These observations demonstrate that exosome release, like autophagy, is negatively regulated by mTORC1 in response to changes in nutrient and growth factor conditions.

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Zou W, Lai M, Zhang Y, Zheng L, Xing Z, Li T et al. Exosome Release Is Regulated by mTORC1. Advanced Science. 2019 Feb 6;6(3). 1801313. https://doi.org/10.1002/advs.201801313