The transition from a rural to an urban environment in Africa alters G protein-coupled receptor signaling

Urbanization in Africa is associated with an increased incidence of non-communicable diseases, yet the cause and the mechanism remain poorly understood. Here, we propose a role for G protein-coupled receptor (GPCR) signaling in the biological changes that occur with urbanization and suggest a critical area of convergence in GPCR signaling might provide a molecular signature for exposure to environmental factors. As a first step in investing this hypothesis, we examined the expression of the G protein α, β and γ subunit, G protein related kinase, and β-arrestin genes in a rural and urban population living in Morocco (NCBI GSE8847). Three genes associated with the phosphatidylinositol signaling pathway (GNAQ, GNA11 and GNA15), and one gene controlling the cyclic adenosine monophosphate pathway (GNAI2) was altered by urbanization. Of note, the expression of ARRB1 gene, which encodes the β-arrestin 1 protein and dampens the cellular responses to extracellular signals, was greater in the rural compared to the urban population (P < 0.00002). These preliminary findings support our hypothesis that urbanization fundamentally alters GPCR signaling, resulting in both a qualitative and quantitative change in the signaling process. Because GPCR signaling is involved in a broad spectrum of cellular functions, further research is needed confirm these preliminary findings and to investigate what role GPCRs might have in the biological changes that occur with urbanization.