- 著者
- Takahide Matsui Yuriko Sakamaki Shu Hiragi Mitsunori Fukuda
- 出版者
- Japan Society for Cell Biology
- 雑誌
- Cell Structure and Function (ISSN:03867196)
- 巻号頁・発行日
- pp.23067, (Released:2023-09-14)
- 被引用文献数
- 2
Small extracellular vesicles (sEVs) are largely classified into two types, plasma-membrane derived sEVs and endomembrane-derived sEVs. The latter type (referred to as exosomes herein) is originated from late endosomes or multivesicular bodies (MVBs). In order to release exosomes extracellularly, MVBs must fuse with the plasma membrane, not with lysosomes. In contrast to the mechanism responsible for MVB–lysosome fusion, the mechanism underlying the MVB–plasma membrane fusion is poorly understood. Here, we systematically analyze soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) family proteins and identify VAMP5 as an MVB-localized SNARE protein required for exosome release. Depletion of VAMP5 in HeLa cells impairs exosome release. Mechanistically, VAMP5 mediates exosome release by interacting with SNAP47 and plasma membrane SNARE Syntaxin 1 (STX1) or STX4 to release exosomes. VAMP5 is also found to mediate asymmetric exosome release from polarized Madin-Darby canine kidney (MDCK) epithelial cells through interaction with the distinct sets of Q-SNAREs, suggesting that VAMP5 is a general exosome regulator in both polarized cells and non-polarized cells.Key words: Exosome, small extracellular vesicle (sEV), multivesicular body, SNARE, VAMP5
- 著者
- Hayashi Yamamoto Takahide Matsui
- 出版者
- The Medical Association of Nippon Medical School
- 雑誌
- Journal of Nippon Medical School (ISSN:13454676)
- 巻号頁・発行日
- pp.JNMS.2024_91-102, (Released:2023-06-02)
- 被引用文献数
- 9
Autophagy is a self-digestive process that is conserved in eukaryotic cells and responsible for maintaining cellular homeostasis through proteolysis. By this process, cells break down their own components in lysosomes. Autophagy can be classified into three categories: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Macroautophagy involves membrane elongation and microautophagy involves membrane internalization, and both pathways undergo selective or non-selective processes that transport cytoplasmic components into lysosomes to be degraded. CMA, however, involves selective incorporation of cytosolic materials into lysosomes without membrane deformation. All three categories of autophagy have attracted much attention due to their involvement in various biological phenomena and their relevance to human diseases, such as neurodegenerative diseases and cancer. Clarification of the molecular mechanisms behind these processes is key to understanding autophagy and recent studies have made major progress in this regard, especially for the mechanisms of initiation and membrane elongation in macroautophagy and substrate recognition in microautophagy and CMA. Furthermore, it is becoming evident that the three categories of autophagy are related to each other despite their implementation by different sets of proteins and the involvement of completely different membrane dynamics. In this review, recent progress in macroautophagy, microautophagy, and CMA are summarized.