Reciprocal Regulation of Chaperone-Mediated Autophagy/Microautophagy and Exosome Release

• Oshima Mutsumi

  Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University

• Seki Takahiro

  Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University

• Kurauchi Yuki

  Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University

• Hisatsune Akinori

  Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University Priority Organization for Innovation and Excellence, Kumamoto University Program for Leading Graduate Schools “HIGO (Health life science: Interdisciplinary and Glocal Oriented) Program,” Kumamoto University

• Katsuki Hiroshi

  Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University

Abstract

Autophagy-lysosome proteolysis is involved in protein quality control and classified into macroautophagy (MA), microautophagy (mA) and chaperone-mediated autophagy (CMA), by the routes of substrate delivery to lysosomes. Both autophagy-lysosome proteolysis and exosome release are strongly associated with membrane trafficking. In the present study, we investigated how chemical and small interfering RNA (siRNA)-mediated activation and inhibition of these autophagic pathways affect exosome release in AD293 cells. Activation of MA and mA by rapamycin and activation of CMA by mycophenolic acid significantly decreased exosome release. Although lysosomal inhibitors, NH₄Cl and bafilomycin A1, significantly increased exosome release, a MA inhibitor, 3-methyladenine, did not affect. Exosome release was significantly increased by the siRNA-mediated knockdown of LAMP2A, which is crucial for CMA. Inversely, activity of CMA/mA was significantly increased by the prevention of exosome release, which was induced by siRNA-mediated knockdown of Rab27a. These findings indicate that CMA/mA and exosome release are reciprocally regulated. This regulation would be the molecular basis of extracellular release and propagation of misfolded proteins in various neurodegenerative diseases.

Journal

• Biological and Pharmaceutical Bulletin

  Biological and Pharmaceutical Bulletin 42 (8), 1394-1401, 2019-08-01

  The Pharmaceutical Society of Japan

Keywords

• exosome
• chaperone-mediated autophagy
• microautophagy
• macroautophagy

Details

• CRID: 1390001288155387648
• NII Article ID: 130007686728
• NII Book ID: AA10885497
• DOI: 10.1248/bpb.b19-00316
• ISSN: 13475215
• ISSN: 09186158
• NDL BIB ID: 029840839
• PubMed: 31366874
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I029840839
• Web Site: https://www.jstage.jst.go.jp/article/bpb/42/8/42_b19-00316/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2020123156
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed