| Title: | Development of new tools to study membrane-anchored mammalian Atg8 proteins |
| Authors: | Park, Sang-Won Browse this author |
| Jeon, Pureum Browse this author |
| Yamasaki, Akinori Browse this author |
| Lee, Hye Eun Browse this author |
| Choi, Haneul Browse this author |
| Mun, Ji Young Browse this author |
| Jun, Yong-Woo Browse this author |
| Park, Ju-Hui Browse this author |
| Lee, Seung-Hwan Browse this author |
| Lee, Soo-Kyeong Browse this author |
| Lee, You-Kyung Browse this author |
| Song, Hyun Kyu Browse this author |
| Lazarou, Michael Browse this author |
| Cho, Dong-Hyong Browse this author |
| Komatsu, Masaaki Browse this author |
| Noda, Nobuo N. Browse this author |
| Jang, Deok-Jin Browse this author |
| Lee, Jin-A Browse this author |
| Keywords: | Autophagy |
| GABARAP |
| LIR motif |
| mammalian ATG8 |
| RavZ protein |
| selective mATG8-PE delipidation |
| Issue Date: | 4-May-2023 |
| Publisher: | Taylor & Francis |
| Journal Title: | Autophagy |
| Volume: | 19 |
| Issue: | 5 |
| Start Page: | 1424 |
| End Page: | 1443 |
| Publisher DOI: | 10.1080/15548627.2022.2132040 |
| Abstract: | Mammals conserve multiple mammalian Atg8-family proteins (mATG8s) consisting of GABARAP (GABA type A receptor-associated protein) and MAP1LC3/LC3 (microtubule associated protein 1 light chain 3) subfamilies that tightly bind to autophagic membranes in a membrane-anchored form. These proteins are crucial for selective autophagy and recruit proteins bearing LC3-interacting region (LIR) motifs. However, because limited research tools are available, information on the specific roles of each membrane-anchored mATG8 in selective autophagy is scarce. In this study, we identified LIR motifs specific to the membrane-anchored form of each mATG8 and characterized the residues critical for their selective interaction using cell-based assays and structural analyses. We then used these selective LIR motifs to develop probes and irreversible deconjugases that targeted selective membrane-anchored mATG8s in the autophagic membrane, revealing that membrane-anchored GABARAP subfamily proteins regulate the aggrephagy of amyotrophic lateral sclerosis-linked protein aggregates. Our tools will be useful for elucidating the functional significance of each mATG8 protein on autophagic membranes in autophagy research. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/89407 |
| Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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