MRAP2 inhibits β-arrestin-2 recruitment to the Prokineticin 2 receptor 2

Melanocortin receptor accessory protein 2 (MRAP2) is a membrane protein that binds 11 multiple G protein-coupled receptors (GPCRs), involved in the control of energy homeostasis in- 12 cluding prokineticin receptors. These GPCRs are expressed both centrally and peripherally and 13 their endogenous ligands are prokineticin 1 (PK1) and prokineticin 2 (PK2). PKRs couple all G-pro- 14 tein subtypes such as Gαq/11, Gαs and Gαi and recruit β-arrestins upon PK2 stimulation, although 15 the interaction between PKR2 and β-arrestins does not trigger receptor internalisation. MRAP2 in- 16 hibits the anorexigenic effect of PK2 by binding PKR1 and PKR2. The aim of this work was to eluci- 17 date the role of MRAP2 in modulating PKR2-induced β-arrestin-2 recruitment and β-arrestin-medi- 18 ated signalling. This study could allow the identification of new specific targets for potential new 19 drugs useful for the treatment of the various pathologies correlated with prokineticin, in particular 20 obesity.