Papers of the Week

Transient Receptor Potential Vanilloid 1 (TRPV1) plays a central role in nociception and inflammation-induced hyperalgesia. Prokineticin receptors (PKR1 and PKR2) are G protein-coupled receptors (GPCRs) that are expressed both centrally and peripherally and induce various signalling pathways through the binding of their endogenous ligands, the prokineticins. The activation of PKRs is modulated by interaction with accessory proteins such as snapin and β-arrestin-2. The prokineticin system is involved in the mechanisms of pain perception by triggering a strong hyperalgesia that lowers the thresholds for thermal and mechanical stimuli. PKR1 and PKR2 are both expressed in dorsal root ganglia (DRG) neurons where they colocalise with TRPV1. In this work, we have identified the regions that mediate the physical interaction between TRPV1 and PKR2. We demonstrated that in the presence of the accessory protein snapin, the strength of binding between TRPV1and PKR2 is increased. TRPV1 proves to be a physiological regulator of PKR2, modulating its activation, localisation and β-arrestin binding as well as PK2-induced mechanical allodynia. The results obtained show for the first time that TRPV1 regulates PKR2 signalling, suggesting a bidirectional interaction between the two systems.