Figure 3.

Receptor occupancy dictates cell migratory fate. Single receptor occupancy (i.e., 1:2 ligand–receptor binding) with a CXCL12 monomer promotes activation of both Gα_i and β-arrestin signaling leading to the balanced cycling of phosphorylated myosin light chain (MLC). Single occupancy balanced signaling promotes the formation and cycling of actin stress fibers needed for cell motility. When double, or 2:2, receptor occupancy occurs, β-arrestin signaling remains basally activate while the G protein signaling arm is activated. This leads to a G protein and calcium mobilization dependent increase in AMPK activity and unbalanced cycling of MLC phosphorylation, therefore preventing the organization of actin stress fibers and limited cell migration.