Open AccessExosome Release Is Regulated by mTORC1
Author(s) -
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 ZhongKai,
Jiang Yu,
Bai Xiaochun
Publication year - 2019
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201801313
Subject(s) - mtorc1 , exosome , microvesicles , microbiology and biotechnology , autophagy , intracellular , downregulation and upregulation , extracellular , gtpase , chemistry , small gtpase , biology , microrna , biochemistry , signal transduction , pi3k/akt/mtor pathway , apoptosis , gene
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.