How does GPCR interaction alter calcium channels modulation?

CORDISCO GONZALEZ, SANTIAGO; AGUSTINA,GARCÍA MELANO; MUSTAFÁ, EMILIO ROMÁN; CLARA I MC CARTHY; RODRÍGUEZ, SILVIA S.; EMANNUEL E. BORTOLOTTO; RAINGO, JESICA

Córdoba

Congreso; XXV Annual Meeting of the Argentinian Society for Neuroscience Research; 2020

Sociedad Argentina de investigaciones en Neurociencias

Several G protein-coupled receptors (GPCR) are able to form homo or heteromers. Currently, there is an increasing amount of information about dramatic changes in the GPCR activity level and signaling cascades when receptor-receptor interaction occurs. Our laboratory is dedicated to understand the impact of voltage-gated calcium channel (CaV) regulation in neuronal function. We have studied the role of GPCR-mediated modulation of several CaV subtypes. Our current aim is to uncover the dramatic changes in this modulation due to hetero and homomerization of GPCRs. Here, we will present several pieces of evidence suggesting that dopamine receptor type 2 (D2R) and ghrelin receptor (Growth Hormone Secretagogue Receptor, GHSR) heteromers, dopamine receptor type 1 (D1R) and GHSR heteromers, GHSR homodimers and D1R homodimers have a unique effect on CaV activity. Using different experimental approaches, we investigate the effect of GPCR dimerization on their agonist-dependent activity as well as the basal effect due to constitutive activity of the GPCR. In this line we test compounds reported as inverse agonists and GPCR mutants (lacking of constitutive activity) to block or reduce the GPCRs interaction and/or their constitutive activity. GPCRs heteromers have a profound impact on CaV function and this GPCRs interaction could produce novel signaling pathways for the modulation of CaV.