A SPOPL/Cullin-3 ubiquitin ligase complex regulates endocytic trafficking by targeting EPS15 at endosomes
Cullin-3 (CUL3)-based ubiquitin ligases regulate endosome maturation and trafficking of endocytic cargo to lysosomes in mammalian cells. Here, we report that these functions depend on SPOPL, a substrate-specific CUL3 adaptor. We find that SPOPL associates with endosomes and is required for both the...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/13841 |
| _version_ | 1829096996688887808 |
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| author | Michaela Gschweitl Anna Ulbricht Christopher A Barnes Radoslav I Enchev Ingrid Stoffel-Studer Nathalie Meyer-Schaller Jatta Huotari Yohei Yamauchi Urs F Greber Ari Helenius Matthias Peter |
| author_facet | Michaela Gschweitl Anna Ulbricht Christopher A Barnes Radoslav I Enchev Ingrid Stoffel-Studer Nathalie Meyer-Schaller Jatta Huotari Yohei Yamauchi Urs F Greber Ari Helenius Matthias Peter |
| author_sort | Michaela Gschweitl |
| collection | DOAJ |
| description | Cullin-3 (CUL3)-based ubiquitin ligases regulate endosome maturation and trafficking of endocytic cargo to lysosomes in mammalian cells. Here, we report that these functions depend on SPOPL, a substrate-specific CUL3 adaptor. We find that SPOPL associates with endosomes and is required for both the formation of multivesicular bodies (MVBs) and the endocytic host cell entry of influenza A virus. In SPOPL-depleted cells, endosomes are enlarged and fail to acquire intraluminal vesicles (ILVs). We identify a critical substrate ubiquitinated by CUL3-SPOPL as EPS15, an endocytic adaptor that also associates with the ESCRT-0 complex members HRS and STAM on endosomes. Indeed, EPS15 is ubiquitinated in a SPOPL-dependent manner, and accumulates with HRS in cells lacking SPOPL. Together, our data indicates that a CUL3-SPOPL E3 ubiquitin ligase complex regulates endocytic trafficking and MVB formation by ubiquitinating and degrading EPS15 at endosomes, thereby influencing influenza A virus infection as well as degradation of EGFR and other EPS15 targets. |
| first_indexed | 2024-04-11T09:06:41Z |
| format | Article |
| id | doaj.art-fa99aac19d8e409182937149300f333a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:06:41Z |
| publishDate | 2016-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-fa99aac19d8e409182937149300f333a2022-12-22T04:32:37ZengeLife Sciences Publications LtdeLife2050-084X2016-03-01510.7554/eLife.13841A SPOPL/Cullin-3 ubiquitin ligase complex regulates endocytic trafficking by targeting EPS15 at endosomesMichaela Gschweitl0Anna Ulbricht1Christopher A Barnes2Radoslav I Enchev3Ingrid Stoffel-Studer4Nathalie Meyer-Schaller5Jatta Huotari6Yohei Yamauchi7Urs F Greber8Ari Helenius9Matthias Peter10https://orcid.org/0000-0002-2160-6824Institute of Biochemistry, Department of Biology, Eidgenössische Technische Hochschule Zürich, Zurich, SwitzerlandInstitute of Biochemistry, Department of Biology, Eidgenössische Technische Hochschule Zürich, Zurich, SwitzerlandInstitute of Biochemistry, Department of Biology, Eidgenössische Technische Hochschule Zürich, Zurich, SwitzerlandInstitute of Biochemistry, Department of Biology, Eidgenössische Technische Hochschule Zürich, Zurich, SwitzerlandInstitute of Biochemistry, Department of Biology, Eidgenössische Technische Hochschule Zürich, Zurich, SwitzerlandInstitute of Biochemistry, Department of Biology, Eidgenössische Technische Hochschule Zürich, Zurich, SwitzerlandInstitute of Biochemistry, Department of Biology, Eidgenössische Technische Hochschule Zürich, Zurich, SwitzerlandInstitute of Molecular Life Sciences, University of Zurich, Zurich, SwitzerlandInstitute of Molecular Life Sciences, University of Zurich, Zurich, SwitzerlandInstitute of Biochemistry, Department of Biology, Eidgenössische Technische Hochschule Zürich, Zurich, SwitzerlandInstitute of Biochemistry, Department of Biology, Eidgenössische Technische Hochschule Zürich, Zurich, SwitzerlandCullin-3 (CUL3)-based ubiquitin ligases regulate endosome maturation and trafficking of endocytic cargo to lysosomes in mammalian cells. Here, we report that these functions depend on SPOPL, a substrate-specific CUL3 adaptor. We find that SPOPL associates with endosomes and is required for both the formation of multivesicular bodies (MVBs) and the endocytic host cell entry of influenza A virus. In SPOPL-depleted cells, endosomes are enlarged and fail to acquire intraluminal vesicles (ILVs). We identify a critical substrate ubiquitinated by CUL3-SPOPL as EPS15, an endocytic adaptor that also associates with the ESCRT-0 complex members HRS and STAM on endosomes. Indeed, EPS15 is ubiquitinated in a SPOPL-dependent manner, and accumulates with HRS in cells lacking SPOPL. Together, our data indicates that a CUL3-SPOPL E3 ubiquitin ligase complex regulates endocytic trafficking and MVB formation by ubiquitinating and degrading EPS15 at endosomes, thereby influencing influenza A virus infection as well as degradation of EGFR and other EPS15 targets.https://elifesciences.org/articles/13841endocytosisinfluenza A virusEGFRCUL3SPOPLEPS15 |
| spellingShingle | Michaela Gschweitl Anna Ulbricht Christopher A Barnes Radoslav I Enchev Ingrid Stoffel-Studer Nathalie Meyer-Schaller Jatta Huotari Yohei Yamauchi Urs F Greber Ari Helenius Matthias Peter A SPOPL/Cullin-3 ubiquitin ligase complex regulates endocytic trafficking by targeting EPS15 at endosomes eLife endocytosis influenza A virus EGFR CUL3 SPOPL EPS15 |
| title | A SPOPL/Cullin-3 ubiquitin ligase complex regulates endocytic trafficking by targeting EPS15 at endosomes |
| title_full | A SPOPL/Cullin-3 ubiquitin ligase complex regulates endocytic trafficking by targeting EPS15 at endosomes |
| title_fullStr | A SPOPL/Cullin-3 ubiquitin ligase complex regulates endocytic trafficking by targeting EPS15 at endosomes |
| title_full_unstemmed | A SPOPL/Cullin-3 ubiquitin ligase complex regulates endocytic trafficking by targeting EPS15 at endosomes |
| title_short | A SPOPL/Cullin-3 ubiquitin ligase complex regulates endocytic trafficking by targeting EPS15 at endosomes |
| title_sort | spopl cullin 3 ubiquitin ligase complex regulates endocytic trafficking by targeting eps15 at endosomes |
| topic | endocytosis influenza A virus EGFR CUL3 SPOPL EPS15 |
| url | https://elifesciences.org/articles/13841 |
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