Phosphorylation and ubiquitylation are opposing players in regulating endocytosis of the water channel Aquaporin-2
| Autor: | Joachim Slengerik-Hansen, Hanne B. Moeller, Trairak Pisitkun, Robert A. Fenton, Takwa S. Aroankins |
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| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | Journal of Cell Science. |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.150680 |
| Popis: | The post-translational modifications (PTMs) phosphorylation and ubiquitylation regulate plasma membrane protein function. Here we examine interplay between phosphorylation and ubiquitylation of the membrane protein aquaporin-2 (AQP2) and demonstrate that phosphorylation can override the previously suggested dominant endocytic signal of K63-linked polyubiquitylation. In polarized epithelial cells, although Ser-256 is an important phosphorylation site for AQP2 membrane localization, the rate of AQP2 endocytosis was reduced by prolonging phosphorylation specifically at Ser-269. Despite close association, AQP2 phosphorylation at Ser-269 and ubiquitylation at Lys-270 can occur in parallel, with increased Ser-269 phosphorylation and decreased AQP2 endocytosis occurring when Lys-270 polyubiquitylation levels are maximal. In vivo studies support this data, with maximal levels of AQP2 ubiquitylation occuring in parallel to maximal Ser-269 phosphorylation and enhanced AQP2 plasma membrane localization. In conclusion, we demonstrate for the first time that although K63-linked polyubiquitylation marks AQP2 for endocytosis, site-specific phosphorylation can counteract polyubiquitylation to determine its final localization. Similar mechanisms may exist for other plasma membrane proteins. |
| Databáze: | OpenAIRE |
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