Crosstalk within GPCR Heteromers in Schizophrenia and Parkinsons Disease: Physical or Just Functional?

R.      Guixa-Gonzalez; A.      Bruno; M.      Marti-Solano; J.      Selent

Abstract

Crosstalk between G protein-coupled receptors (GPCRs) is one of the key mechanisms used by the cell for integrating multiple signaling pathways. Functional crosstalk at the level of signaling pathways was initially thought to regulate receptor function. Importantly, the existence of GPCR heteromers demonstrates that direct physical interactions between GPCRs could also be behind the crosstalk phenomenon. Neurological disorders such as Parkinsons disease (PD) and schizophrenia have been linked to a dysfunctional communication between certain GPCRs. In this review, we discuss functional and physical crosstalk of the main GPCR families involved in the aforementioned disorders. In addition, we analyze the available structural information on physical crosstalk and highlight some strategies in drug discovery based on these crosstalk mechanisms.

Keywords: Dimerisation, drug discovery, GPCR, heteromers, receptor crosstalk, receptor signaling, Parkinson disease, schizophrenia, Neurological disorders, crosstalk mechanisms