Thioredoxin-related transmembrane protein 2 (TMX2) regulates the Ran protein gradient and importin-β-dependent nuclear cargo transport
Abstract TMX2 is a thioredoxin family protein, but its functions have not been clarified. To elucidate the function of TMX2, we explored TMX2-interacting proteins by LC-MS. As a result, importin-β, Ran GTPase (Ran), RanGAP, and RanBP2 were identified. Importin-β is an adaptor protein which imports c...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2019-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-019-51773-x |
| _version_ | 1818995087239020544 |
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| author | Ami Oguro Susumu Imaoka |
| author_facet | Ami Oguro Susumu Imaoka |
| author_sort | Ami Oguro |
| collection | DOAJ |
| description | Abstract TMX2 is a thioredoxin family protein, but its functions have not been clarified. To elucidate the function of TMX2, we explored TMX2-interacting proteins by LC-MS. As a result, importin-β, Ran GTPase (Ran), RanGAP, and RanBP2 were identified. Importin-β is an adaptor protein which imports cargoes from cytosol to the nucleus, and is exported into the cytosol by interaction with RanGTP. At the cytoplasmic nuclear pore, RanGAP and RanBP2 facilitate hydrolysis of RanGTP to RanGDP and the disassembly of the Ran-importin-β complex, which allows the recycling of importin-β and reentry of Ran into the nucleus. Despite its interaction of TMX2 with importin-β, we showed that TMX2 is not a transport cargo. We found that TMX2 localizes in the outer nuclear membrane with its N-terminus and C-terminus facing the cytoplasm, where it co-localizes with importin-β and Ran. Ran is predominantly distributed in the nucleus, but TMX2 knockdown disrupted the nucleocytoplasmic Ran gradient, and the cysteine 112 residue of Ran was important in its regulation by TMX2. In addition, knockdown of TMX2 suppressed importin-β-mediated transport of protein. These results suggest that TMX2 works as a regulator of protein nuclear transport, and that TMX2 facilitates the nucleocytoplasmic Ran cycle by interaction with nuclear pore proteins. |
| first_indexed | 2024-12-20T21:08:16Z |
| format | Article |
| id | doaj.art-9863a50a207247c2af1fce0da2dabf5c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T21:08:16Z |
| publishDate | 2019-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-9863a50a207247c2af1fce0da2dabf5c2022-12-21T19:26:34ZengNature PortfolioScientific Reports2045-23222019-10-019111310.1038/s41598-019-51773-xThioredoxin-related transmembrane protein 2 (TMX2) regulates the Ran protein gradient and importin-β-dependent nuclear cargo transportAmi Oguro0Susumu Imaoka1Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin UniversityDepartment of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin UniversityAbstract TMX2 is a thioredoxin family protein, but its functions have not been clarified. To elucidate the function of TMX2, we explored TMX2-interacting proteins by LC-MS. As a result, importin-β, Ran GTPase (Ran), RanGAP, and RanBP2 were identified. Importin-β is an adaptor protein which imports cargoes from cytosol to the nucleus, and is exported into the cytosol by interaction with RanGTP. At the cytoplasmic nuclear pore, RanGAP and RanBP2 facilitate hydrolysis of RanGTP to RanGDP and the disassembly of the Ran-importin-β complex, which allows the recycling of importin-β and reentry of Ran into the nucleus. Despite its interaction of TMX2 with importin-β, we showed that TMX2 is not a transport cargo. We found that TMX2 localizes in the outer nuclear membrane with its N-terminus and C-terminus facing the cytoplasm, where it co-localizes with importin-β and Ran. Ran is predominantly distributed in the nucleus, but TMX2 knockdown disrupted the nucleocytoplasmic Ran gradient, and the cysteine 112 residue of Ran was important in its regulation by TMX2. In addition, knockdown of TMX2 suppressed importin-β-mediated transport of protein. These results suggest that TMX2 works as a regulator of protein nuclear transport, and that TMX2 facilitates the nucleocytoplasmic Ran cycle by interaction with nuclear pore proteins.https://doi.org/10.1038/s41598-019-51773-x |
| spellingShingle | Ami Oguro Susumu Imaoka Thioredoxin-related transmembrane protein 2 (TMX2) regulates the Ran protein gradient and importin-β-dependent nuclear cargo transport Scientific Reports |
| title | Thioredoxin-related transmembrane protein 2 (TMX2) regulates the Ran protein gradient and importin-β-dependent nuclear cargo transport |
| title_full | Thioredoxin-related transmembrane protein 2 (TMX2) regulates the Ran protein gradient and importin-β-dependent nuclear cargo transport |
| title_fullStr | Thioredoxin-related transmembrane protein 2 (TMX2) regulates the Ran protein gradient and importin-β-dependent nuclear cargo transport |
| title_full_unstemmed | Thioredoxin-related transmembrane protein 2 (TMX2) regulates the Ran protein gradient and importin-β-dependent nuclear cargo transport |
| title_short | Thioredoxin-related transmembrane protein 2 (TMX2) regulates the Ran protein gradient and importin-β-dependent nuclear cargo transport |
| title_sort | thioredoxin related transmembrane protein 2 tmx2 regulates the ran protein gradient and importin β dependent nuclear cargo transport |
| url | https://doi.org/10.1038/s41598-019-51773-x |
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