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: Article

27 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 originalEnglish
Páginas (desde-hasta)4463-4474
Número de páginas12
PublicaciónJournal of Cell Science
Volumen125
N.º19
DOI
EstadoPublished - 2012

Huella dactilar

Chemokine Receptors
Ubiquitination
Cell Movement
trans-Golgi Network
Ligands
Recycling
Chemokines
Dendritic Cells
Immune System
Cell Membrane
Lymphocytes

ASJC Scopus subject areas

  • Cell Biology

Citar esto

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
Schaeuble, Karin ; Hauser, Mark A. ; Rippl, Alexandra V. ; Bruderer, Roland ; Otero, Carolina ; Groettrup, Marcus ; Legler, Daniel F. / Ubiquitylation of the chemokine receptor CCR7 enables efficient receptor recycling and cell migration. En: Journal of Cell Science. 2012 ; Vol. 125, N.º 19. pp. 4463-4474.
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abstract = "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.",
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Schaeuble, K, Hauser, MA, Rippl, AV, Bruderer, R, Otero, C, Groettrup, M & Legler, DF 2012, 'Ubiquitylation of the chemokine receptor CCR7 enables efficient receptor recycling and cell migration', Journal of Cell Science, vol. 125, n.º 19, pp. 4463-4474. https://doi.org/10.1242/jcs.097519

Ubiquitylation of the chemokine receptor CCR7 enables efficient receptor recycling and cell migration. / Schaeuble, Karin; Hauser, Mark A.; Rippl, Alexandra V.; Bruderer, Roland; Otero, Carolina; Groettrup, Marcus; Legler, Daniel F.

En: Journal of Cell Science, Vol. 125, N.º 19, 2012, p. 4463-4474.

Resultado de la investigación: Article

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T1 - Ubiquitylation of the chemokine receptor CCR7 enables efficient receptor recycling and cell migration

AU - Schaeuble, Karin

AU - Hauser, Mark A.

AU - Rippl, Alexandra V.

AU - Bruderer, Roland

AU - Otero, Carolina

AU - Groettrup, Marcus

AU - Legler, Daniel F.

PY - 2012

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N2 - 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.

AB - 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.

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