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RAMP3 determines rapid recycling of atypical chemokine receptor-3 for guided angiogenesis

2019; National Academy of Sciences; Volume: 116; Issue: 48 Linguagem: Inglês

10.1073/pnas.1905561116

1091-6490

Duncan I. Mackie, Natalie R. Nielsen, Matthew Harris, Smriti Singh, Reema B. Davis, Danica Dy, Graham Ladds, Kathleen M. Caron,

Cell Adhesion Molecules Research

Significance G-protein–coupled receptors (GPCRs) exist within multi-protein complexes on the surface of cells in order to respond to a wide variety of extracellular stimuli such as neurotransmitters, migratory cues, hormones, light, and odors. In this study, we discover and characterize an expanded repertoire of GPCRs that interact with receptor-activity–modifying proteins (RAMPs)—a class of proteins that can modulate the type and consequences of extracellular signals to GPCRs. Specifically, we find that RAMP interaction with chemokine GPCRs is essential for enabling these receptors to bind and degrade extracellular migratory cues and thereby establish gradients for directed cellular migration. In the absence of these critical proteins, the process of blood vessel sprouting within the postnatal retina is dysfunctional.