Chemokine Receptor CCR7 Triggers an Endomembrane Signaling Complex for Spatial Rac Activation

Laufer, Julia M.; Hauser, Mark A.; Kindinger, Ilona; Purvanov, Vladimir; Pauli, Andreas; Legler, Daniel F.

Chemokine Receptor CCR7 Triggers an Endomembrane Signaling Complex for Spatial Rac Activation

Dateien

Laufer_2-joqri52zvsvz5.pdfGröße: 6.38 MBDownloads: 350

Datum

2019

Autor:innen

Kindinger, Ilona

Pauli, Andreas

Open Access-Veröffentlichung

Open Access Gold

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Cell Reports. 2019, 29(4), pp. 995-1009.e6. eISSN 2211-1247. Available under: doi: 10.1016/j.celrep.2019.09.031

Zusammenfassung

Chemokine-guided cell migration is pivotal for many immunological and developmental processes. How chemokine receptor signaling persists to guarantee sustained directional migration despite receptor desensitization and internalization remains poorly understood. Here, we uncover a function for an intracellular pool of the chemokine receptor CCR7 present in human dendritic cells and cellular model systems. We find that CCR7 signaling, initiated at the plasma membrane, is translocated by joint trafficking of β-arrestin and Src kinase to endomembrane-residing CCR7. There, Src tyrosine phosphorylates CCR7, required for the recruitment of Vav1 to form an endomembrane-residing multi-protein signaling complex comprising CCR7, the RhoGEF Vav1, and its effector, Rac1. Interfering with vesicular trafficking affects CCR7-driven cell migration, whereas CCR7:Vav1 interaction at endomembranes is essential for local Rac1 recruitment to CCR7. Photoactivation of Rac1 at endomembranes leads to lamellipodia formation at the cell's leading edge, supporting the role of sustained endomembrane signaling in guiding cell migration.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

LAUFER, Julia M., Mark A. HAUSER, Ilona KINDINGER, Vladimir PURVANOV, Andreas PAULI, Daniel F. LEGLER, 2019. Chemokine Receptor CCR7 Triggers an Endomembrane Signaling Complex for Spatial Rac Activation. In: Cell Reports. 2019, 29(4), pp. 995-1009.e6. eISSN 2211-1247. Available under: doi: 10.1016/j.celrep.2019.09.031

BibTex

@article{Laufer2019-10-22Chemo-47331,
  year={2019},
  doi={10.1016/j.celrep.2019.09.031},
  title={Chemokine Receptor CCR7 Triggers an Endomembrane Signaling Complex for Spatial Rac Activation},
  number={4},
  volume={29},
  journal={Cell Reports},
  pages={995--1009.e6},
  author={Laufer, Julia M. and Hauser, Mark A. and Kindinger, Ilona and Purvanov, Vladimir and Pauli, Andreas and Legler, Daniel F.}
}

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