The chemokine/chemokine receptor system is essential for guiding cell migration in health and disease. Chemokines and their receptors have emerged as key players and therapeutic targets not only in immune and inflammatory disorders, but also in cancer. Chemokine receptors belong to the large and versatile family of seven-transmembrane domain, G protein-coupled receptors (GPCRs) that activate multiple signal transduction pathways to orchestrate cell migration.
The chemokine receptor CCR7together with its ligands CCL19 and CCL21are prominent players in guiding antigen-loaded dendritic cells and lymphocytes to lymphoid organs to launch specific immune responses against invading pathogens. Moreover, the CCR7-CCL19/CCL21-axis is also involved in thymic development, tolerance induction and in cancer metastasis. A major research aim is to decipher molecular mechanisms how distinct CCR7 signaling pathways initiated at the plasma membrane by the two ligands CCL19 and CCL21 enable efficient and sustained cell locomotion.
Atypical chemokine receptors(ACKRs) contribute to the cell migration process by binding, internalizing and degrading local chemokines, which enables the formation of confined chemokine gradients. The atypical chemokine receptor ACKR4internalizes and scavenges the homing chemokines CCL19, CCL21, and CCL25, and thereby shape functional chemokine gradients. Our research focuses on how ACKR4 scavenges chemokines and which intracellular trafficking routes account for the continuous internalization and recycling of the receptor.
