p62/SQSTM1 promotes rapid ubiquitin conjugation to target proteins after endosome rupture during xenophagy
Autophagy is a bulk degradation pathway, and selective autophagy to remove foreign entities is called xenophagy. The conjugation of ubiquitin to target pathogens is an important process in xenophagy but when and where this ubiquitination occurs remains unclear. Here, we analyzed the temporal sequenc...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2018-03-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.12385 |
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| _version_ | 1846108009571287040 |
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| author | Megumi Tsuchiya Hidesato Ogawa Takako Koujin Chie Mori Hiroko Osakada Shouhei Kobayashi Yasushi Hiraoka Tokuko Haraguchi |
| author_facet | Megumi Tsuchiya Hidesato Ogawa Takako Koujin Chie Mori Hiroko Osakada Shouhei Kobayashi Yasushi Hiraoka Tokuko Haraguchi |
| author_sort | Megumi Tsuchiya |
| collection | DOAJ |
| description | Autophagy is a bulk degradation pathway, and selective autophagy to remove foreign entities is called xenophagy. The conjugation of ubiquitin to target pathogens is an important process in xenophagy but when and where this ubiquitination occurs remains unclear. Here, we analyzed the temporal sequence and subcellular location of ubiquitination during xenophagy using time‐lapse observations, with polystyrene beads mimicking invading pathogens. Results revealed accumulation of a ubiquitination marker around the beads within 3 min after endosome rupture. Recruitment of ubiquitin to the beads was significantly delayed in p62‐knockout murine embryonic fibroblast cells, and this delay was rescued by ectopic p62 expression. Ectopic expression of a phosphorylation‐mimicking p62 mutated at serine residue 405 (equivalent to human serine residue 403) rescued this delay, but its unphosphorylated form did not. These results indicate that ubiquitination mainly occurs after endosome rupture and suggest that p62, specifically the phosphorylated form, promotes ubiquitin conjugation to target proteins in xenophagy. |
| format | Article |
| id | doaj-art-7b7b1292dd3d4e959b42c96b1f95cae1 |
| institution | Kabale University |
| issn | 2211-5463 |
| language | English |
| publishDate | 2018-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj-art-7b7b1292dd3d4e959b42c96b1f95cae12024-12-26T06:31:12ZengWileyFEBS Open Bio2211-54632018-03-018347048010.1002/2211-5463.12385p62/SQSTM1 promotes rapid ubiquitin conjugation to target proteins after endosome rupture during xenophagyMegumi Tsuchiya0Hidesato Ogawa1Takako Koujin2Chie Mori3Hiroko Osakada4Shouhei Kobayashi5Yasushi Hiraoka6Tokuko Haraguchi7Graduate School of Frontier Biosciences Osaka University Suita JapanGraduate School of Frontier Biosciences Osaka University Suita JapanAdvanced ICT Research Institute Kobe National Institute of Information and Communications Technology Kobe JapanAdvanced ICT Research Institute Kobe National Institute of Information and Communications Technology Kobe JapanAdvanced ICT Research Institute Kobe National Institute of Information and Communications Technology Kobe JapanAdvanced ICT Research Institute Kobe National Institute of Information and Communications Technology Kobe JapanGraduate School of Frontier Biosciences Osaka University Suita JapanGraduate School of Frontier Biosciences Osaka University Suita JapanAutophagy is a bulk degradation pathway, and selective autophagy to remove foreign entities is called xenophagy. The conjugation of ubiquitin to target pathogens is an important process in xenophagy but when and where this ubiquitination occurs remains unclear. Here, we analyzed the temporal sequence and subcellular location of ubiquitination during xenophagy using time‐lapse observations, with polystyrene beads mimicking invading pathogens. Results revealed accumulation of a ubiquitination marker around the beads within 3 min after endosome rupture. Recruitment of ubiquitin to the beads was significantly delayed in p62‐knockout murine embryonic fibroblast cells, and this delay was rescued by ectopic p62 expression. Ectopic expression of a phosphorylation‐mimicking p62 mutated at serine residue 405 (equivalent to human serine residue 403) rescued this delay, but its unphosphorylated form did not. These results indicate that ubiquitination mainly occurs after endosome rupture and suggest that p62, specifically the phosphorylated form, promotes ubiquitin conjugation to target proteins in xenophagy.https://doi.org/10.1002/2211-5463.12385artificial beadsautophagybacterial infectionLC3p62ubiquitination |
| spellingShingle | Megumi Tsuchiya Hidesato Ogawa Takako Koujin Chie Mori Hiroko Osakada Shouhei Kobayashi Yasushi Hiraoka Tokuko Haraguchi p62/SQSTM1 promotes rapid ubiquitin conjugation to target proteins after endosome rupture during xenophagy FEBS Open Bio artificial beads autophagy bacterial infection LC3 p62 ubiquitination |
| title | p62/SQSTM1 promotes rapid ubiquitin conjugation to target proteins after endosome rupture during xenophagy |
| title_full | p62/SQSTM1 promotes rapid ubiquitin conjugation to target proteins after endosome rupture during xenophagy |
| title_fullStr | p62/SQSTM1 promotes rapid ubiquitin conjugation to target proteins after endosome rupture during xenophagy |
| title_full_unstemmed | p62/SQSTM1 promotes rapid ubiquitin conjugation to target proteins after endosome rupture during xenophagy |
| title_short | p62/SQSTM1 promotes rapid ubiquitin conjugation to target proteins after endosome rupture during xenophagy |
| title_sort | p62 sqstm1 promotes rapid ubiquitin conjugation to target proteins after endosome rupture during xenophagy |
| topic | artificial beads autophagy bacterial infection LC3 p62 ubiquitination |
| url | https://doi.org/10.1002/2211-5463.12385 |
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