Abstract
Chemokine signaling is essential for coordinated cell migration in health and disease to specifically govern cell positioning in space and time. Typically, chemokines signal through heptahelical, G protein-coupled receptors to orchestrate cell migration. Notably, chemokine receptors are highly dynamic structures and signaling efficiency largely depends on the discrete contact with the ligand. Promiscuity of both chemokines and chemokine receptors, combined with biased signaling and allosteric modulation of receptor activation, guarantees a tightly controlled recruitment and positioning of individual cells within the local environment at a given time. Here, we discuss recent insights in understanding chemokine gradient formation by atypical chemokine receptors and how typical chemokine receptors can transmit distinct signals to translate guidance cues into coordinated cell locomotion in space and time.
Highlights
Chemokine signaling is essential for coordinated cell migration in health and disease to govern cell positioning in space and time
Chemokine-induced signaling Soon after chemokines were discovered in the late ’80s1–3, it was shown that their cognate receptors on cell surfaces were members of the rhodopsin-like family of G protein–coupled receptors (GPCRs)
Chemokine receptor stimulation leads to the GDP/ GTP exchange of coupled heterotrimeric Gi proteins and the subsequent dissociation of the βγ subunits, which activate phosphoinositide-specific phospholipase Cβ (PLC) and phosphoinositide 3-kinase (PI3K)
Summary
All typical chemokine receptors expressed on leukocyte are able to induce cell migration, the signaling mechanisms downstream of the receptors are not unified. A complex signaling network composed of biased signaling, promiscuous signaling, and signal specificity paired with chemokine presentation and scavenging contributes to chemokine-stimulated cell migration. Such fine tuning is important to allow specific and efficient migration (for example, during immune responses) to guarantee precise spatiotemporal localization of individual effector cells. Competing interests The authors declare that they have no competing interests. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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