Heterodimerization of β(2 )adrenergic receptor and somatostatin receptor 5: Implications in modulation of signaling pathway

BACKGROUND: In the present study, we describe heterodimerization between human-Somatostatin Receptor 5 (hSSTR5) and β(2)-Adrenergic Receptor (β(2)AR) and its impact on the receptor trafficking, coupling to adenylyl cyclase and signaling including mitogen activated protein kinases and calcineurin-NFAT pathways. METHODS: We used co-immunoprecipitation, photobleaching- fluorescence resonance energy transfer and Fluorescence assisted cell sorting analysis to characterize heterodimerization between SSTR5 and β(2)AR. RESULTS: Our results indicate that hSSTR5/β(2)AR exist as preformed heterodimers in the basal condition which is enhanced upon co-activation of both receptors. In contrast, the activation of individual receptors leads to the dissociation of heterodimers. Receptor coupling to adenylyl cyclase displayed predominant effect of β(2)AR, however, somatostatin mediated inhibition of cAMP was enhanced upon blocking β(2)AR. Our results indicate hSSTR5 mediated significant activation of ERK1/2 and inhibition of phospho-p38. The phospho-NFAT level was enhanced in cotransfected cells indicating the blockade of calcineurin mediated dephosphorylation of NFAT upon receptor heterodimerization. CONCLUSION: These data for the first time unveil a novel insight for the role of hSSTR5/β(2)AR in the modulation of signaling pathways which has not been addressed earlier.