Ubiquitylation of the chemokine receptor CCR7 enables efficient receptor recycling and cell migration

Karin Schaeuble, Mark A. Hauser, Alexandra V. Rippl, Roland Bruderer, Carolina Otero, Marcus Groettrup, Daniel F. Legler

Resultado de la investigación: Contribución a una revistaArtículo

30 Citas (Scopus)

Resumen

The chemokine receptor CCR7 is essential for lymphocyte and dendritic cell homing to secondary lymphoid organs. Owing to the ability to induce directional migration, CCR7 and its ligands CCL19 and CCL21 are pivotal for the regulation of the immune system. Here, we identify a novel function for receptor ubiquitylation in the regulation of the trafficking process of this G-protein-coupled seven transmembrane receptor. We discovered that CCR7 is ubiquitylated in a constitutive, ligand-independent manner and that receptor ubiquitylation regulates the basal trafficking of CCR7 in the absence of chemokine. Upon CCL19 binding, we show that internalized CCR7 recycles back to the plasma membrane via the trans-Golgi network. An ubiquitylation-deficient CCR7 mutant internalized normally after ligand binding, but inefficiently recycled in immune cells and was transiently retarded in the trans-Golgi network compartment of HEK293 transfectants. Finally, we demonstrate that the lack of CCR7 ubiquitylation profoundly impairs immune cell migration. Our results provide evidence for a novel function of receptor ubiquitylation in the regulation of CCR7 recycling and immune cell migration.

Idioma originalInglés
Páginas (desde-hasta)4463-4474
Número de páginas12
PublicaciónJournal of Cell Science
Volumen125
N.º19
DOI
EstadoPublicada - 2012

Áreas temáticas de ASJC Scopus

  • Biología celular

Huella Profundice en los temas de investigación de 'Ubiquitylation of the chemokine receptor CCR7 enables efficient receptor recycling and cell migration'. En conjunto forman una huella única.

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    Schaeuble, K., Hauser, M. A., Rippl, A. V., Bruderer, R., Otero, C., Groettrup, M., & Legler, D. F. (2012). Ubiquitylation of the chemokine receptor CCR7 enables efficient receptor recycling and cell migration. Journal of Cell Science, 125(19), 4463-4474. https://doi.org/10.1242/jcs.097519