論文 - 詳細
| RRC ID | 50075 |
|---|---|
| 著者 | Kovačević I, Sakaue T, Majoleé J, Pronk MC, Maekawa M, Geerts D, Fernandez-Borja M, Higashiyama S, Hordijk PL. |
| タイトル | The Cullin-3-Rbx1-KCTD10 complex controls endothelial barrier function via K63 ubiquitination of RhoB. |
| ジャーナル | J Cell Biol |
| Abstract |
RhoGTPases control endothelial cell (EC) migration, adhesion, and barrier formation. Whereas the relevance of RhoA for endothelial barrier function is widely accepted, the role of the RhoA homologue RhoB is poorly defined. RhoB and RhoA are 85% identical, but RhoB's subcellular localization and half-life are uniquely different. Here, we studied the role of ubiquitination for the function and stability of RhoB in primary human ECs. We show that the K63 polyubiquitination at lysine 162 and 181 of RhoB targets the protein to lysosomes. Moreover, we identified the RING E3 ligase complex Cullin-3-Rbx1-KCTD10 as key modulator of endothelial barrier integrity via its regulation of the ubiquitination, localization, and activity of RhoB. In conclusion, our data show that ubiquitination controls the subcellular localization and lysosomal degradation of RhoB and thereby regulates the stability of the endothelial barrier through control of RhoB-mediated EC contraction. |
| 巻・号 | 217(3) |
| ページ | 1015-1032 |
| 公開日 | 2018-3-5 |
| DOI | 10.1083/jcb.201606055 |
| PII | jcb.201606055 |
| PMID | 29358211 |
| PMC | PMC5839774 |
| MeSH | Carrier Proteins / genetics Carrier Proteins / metabolism* Cullin Proteins / genetics Cullin Proteins / metabolism* Human Umbilical Vein Endothelial Cells / cytology Human Umbilical Vein Endothelial Cells / metabolism* Humans Potassium Channels, Voltage-Gated / genetics Potassium Channels, Voltage-Gated / metabolism* Ubiquitination* rhoB GTP-Binding Protein / genetics rhoB GTP-Binding Protein / metabolism* |
| IF | 8.811 |
| 引用数 | 13 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 20 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | CSII-CMV-MCS-IRES2-Bsd (RDB04385) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394). |