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.
Division of Pediatric Surgery, Rady Children's Hospital, San Diego, CA 92123, USA; Department of Surgery, School of Medicine, University of California, La Jolla, CA 92093, USA; Center for Investigations of Health and Education Disparities, University of California San Diego, 9500 Gilman Drive, #0739, La Jolla, CA 92093-0739, USA. Electronic address: sbickler@ucsd.edu.
Stephen W
SW
Bickler
Center for Investigations of Health and Education Disparities, University of California San Diego, 9500 Gilman Drive, #0739, La Jolla, CA 92093-0739, USA; Department of Surgery, Naval Medical Center San Diego, San Diego, CA 92134, USA.
Eliel
E
Lizardo
Department of Surgery, School of Medicine, University of California, La Jolla, CA 92093, USA; Center for Investigations of Health and Education Disparities, University of California San Diego, 9500 Gilman Drive, #0739, La Jolla, CA 92093-0739, USA.
David M
DM
Cauvi
Department of Surgery, School of Medicine, University of California, La Jolla, CA 92093, USA; Center for Investigations of Health and Education Disparities, University of California San Diego, 9500 Gilman Drive, #0739, La Jolla, CA 92093-0739, USA; Department of Neurosciences, School of Medicine, University of California, La Jolla, CA 92093, USA.
Antonio
A
De Maio
D000349:Africa; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007107:Immune System; D009018:Morocco; D010766:Phosphorylation; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012424:Rural Population; D015398:Signal Transduction; D014505:Urban Population; D014507:Urbanization; D000071559:beta-Arrestin 1 / Q000378:metabolism; D000071557:beta-Arrestins / Q000378:metabolism
C000605253:ARRB1 protein, human; C554062:GNA11 protein, human; C554061:GNAQ protein, human; D044385:GTP-Binding Protein alpha Subunits; D043562:Receptors, G-Protein-Coupled; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins; C112631:G protein alpha 16; C498015:GNAI2 protein, human; D051960:GTP-Binding Protein alpha Subunit, Gi2; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
Environment; G protein-coupled receptor; Non-communicable disease; Rural; Urban