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Endosomal Chemokine Receptor Signalosomes Regulate Central Mechanisms Underlying Cell Migration

ABSTRACT: Chemokine receptors are GPCRs that regulate chemotactic migration of a wide variety of cells including immune and cancer cells. Most chemokine receptors harbor molecular properties, which are associated with an ability to stimulate G proteins during b-arrestin-mediated internalization into endosomes. As endosomal signaling of certain non-GPCR receptors plays major roles in cell migration, we here investigated the potential role of endosomal chemokine receptor signaling on mechanisms governing this function. Applying cell biological approaches and spatiotemporal-resolved proteome profiling, we demonstrate that the model chemokine receptor CCR7 upon chemokine stimulation recruits G protein and b-arrestin simultaneously enabling internalized receptors to activate G protein from endosomes. Furthermore, endosomal CCR7 uniquely enriches specific Rho-GTPase regulators as compared to plasma membrane CCR7, which correlates with the activity of Rho-GTPase Rac1. As Rac1 drives the formation of membrane protrusions during chemotaxis, our findings suggest an important integrated function of endosomal chemokine receptor signaling in this physiological event.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Beatrix Ueberheide

PROVIDER: MSV000090362 | MassIVE |

REPOSITORIES: MassIVE

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