論文 - 詳細
| RRC ID | 63319 |
|---|---|
| 著者 | Oguro A, Imaoka S. |
| タイトル | Thioredoxin-related transmembrane protein 2 (TMX2) regulates the Ran protein gradient and importin-β-dependent nuclear cargo transport. |
| ジャーナル | Sci Rep |
| 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. |
| 巻・号 | 9(1) |
| ページ | 15296 |
| 公開日 | 2019-10-25 |
| DOI | 10.1038/s41598-019-51773-x |
| PII | 10.1038/s41598-019-51773-x |
| PMID | 31653923 |
| PMC | PMC6814788 |
| MeSH | Active Transport, Cell Nucleus Cell Nucleus / metabolism* Cytoplasm / metabolism HEK293 Cells HeLa Cells Humans Hydrolysis Membrane Proteins / genetics Membrane Proteins / metabolism* Microscopy, Confocal Nuclear Envelope / metabolism Nuclear Pore / metabolism Protein Binding RNA Interference Thioredoxins / genetics Thioredoxins / metabolism* beta Karyopherins / metabolism* ran GTP-Binding Protein / metabolism* |
| IF | 3.998 |
| リソース情報 | |
| 遺伝子材料 | TMX2/pBiFC VN155 (RDB18581) KPNB1-Cherry C pcDNA (RDB18582) Impβ-VC155 pcDNA (RDB18583) KPNB1/Flag pcDNA (RDB18584) KPNB1/pQE80L (RDB18585) Flag(C)-emerin/pcDNA (RDB18586) Ran WT/Flag(N) pcDNA (RDB18587) TMX2 WT/Flag pcDNA (RDB18588) TMX2 isoform2/Flag pcDNA (RDB18589) TMX2 WT/pcDNA (RDB18590) TMX2 isoform2/pcDNA (RDB18591) TMX2/pGEX5X-1 (RDB18592) TMX2 1-309/pGEX (RDB18593) TMX2 310-891/pGEX (RDB18594) TMX2 376-891/pGEX (RDB18595) 1xFlag(N)TMX2/pcDNA (RDB18596) 1xFlag(C)TMX2/pcDNA (RDB18597) 16-Flag-17 TMX2/pcDNA (RDB18598) 56-Flag-57 TMX2/pcDNA (RDB18599) 80-Flag-81 TMX2/pcDNA (RDB18600) 90-Flag-91 TMX2/pcDNA (RDB18601) Ran WT/pQE80L (RDB18602) Ran WT/pBiFC VC (RDB18603) Ran WT/pBiFC VN (RDB18604) PKINES-venusx2-SV40 NLS/pcDNA (RDB18605) PKINES-venusx2-PTHrP NLS/pcDNA (RDB18606) |