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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


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.


  • *Present address: Department of Cell Biology, Pontificia Universidad Católica de Chile, Av. Bernardo O'Higgins 340, Santiago, Chile

  • Funding

    This study was supported in parts by research funding from the Swiss National Science Foundation [grant numbers SNF 31003A-127474/1, SNF 316030-133812]; the Commission for Technology and Innovation [grant number CTI 12516.1 PFLS-LS], the German Research Foundation [grant number GR1517/8-1]; the Thurgauische Stiftung für Wissenschaft und Forschung, the Swiss State Secretariat for Education and Research; the Max Cloëtta Foundation; and the Thurgauische Krebsliga.

  • Supplementary material available online at

  • Accepted June 7, 2012.
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