Ubiquitination of exposed glycoproteins by SCF FBXO27 directs damaged lysosomes for autophagy
| Autor: | Sayaka Yasuda, Toshiharu Fujita, Keiji Tanaka, Yukiko Yoshida, Yasushi Saeki, Maho Hamasaki, Tamotsu Yoshimori, Arisa Murakami, Junko Kawawaki, Noriyuki Matsuda, Kazuhiro Iwai |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
VAMP3 chemistry.chemical_classification Multidisciplinary LAMP2 biology LAMP1 Cell biology 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure Ubiquitin chemistry Biochemistry Lysosome Ubiquitin ligase complex medicine biology.protein CUL1 Glycoprotein |
| Zdroj: | Proceedings of the National Academy of Sciences. 114:8574-8579 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Ubiquitination functions as a signal to recruit autophagic machinery to damaged organelles and induce their clearance. Here, we report the characterization of FBXO27, a glycoprotein-specific F-box protein that is part of the SCF (SKP1/CUL1/F-box protein) ubiquitin ligase complex, and demonstrate that SCFFBXO27 ubiquitinates glycoproteins in damaged lysosomes to regulate autophagic machinery recruitment. Unlike F-box proteins in other SCF complexes, FBXO27 is subject to N-myristoylation, which localizes it to membranes, allowing it to accumulate rapidly around damaged lysosomes. We also screened for proteins that are ubiquitinated upon lysosomal damage, and identified two SNARE proteins, VAMP3 and VAMP7, and five lysosomal proteins, LAMP1, LAMP2, GNS, PSAP, and TMEM192. Ubiquitination of all glycoproteins identified in this screen increased upon FBXO27 overexpression. We found that the lysosomal protein LAMP2, which is ubiquitinated preferentially on lysosomal damage, enhances autophagic machinery recruitment to damaged lysosomes. Thus, we propose that SCFFBXO27 ubiquitinates glycoproteins exposed upon lysosomal damage to induce lysophagy. |
| Databáze: | OpenAIRE |
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