The GPR88, is an orphan receptor expressed in neurons of striatal and cortical brain regions with differential subcellular distribution patterns, by Jorge Diaz

Abstract The GPR88, is an orphan receptor expressed in neurons of Striatal and cortical brain regions with differential subcellular distribution patterns

The GPR88, is an orphan receptor expressed in neurons of Striatal and cortical brain regions with differential subcellular distribution patterns
GPR88 is an orphan G-protein-coupled receptor (GPCR) originally described as a striatal-enriched transcript (Strg/GPR88). We identified GPR88 expression in all the population of striatal GABAergic medium spiny neurons (MSN) which play an important role in psychomotor functions subserved by the cortico-basal ganglia network. Different studies show that genetic deletion of GPR88 in mice leads to altered MSN excitability and striatal dopamine signaling, modified locomotor responses to dopamine agonists as well as reduced motor coordination.
GPR88 expression is also present in cerebral cortex neurons with an atypical nuclear chromatin-associated localization which is established during corticogenesis and remain until adulthood. In a recent study we demonstrated the colocalization of GPR88 with three nuclear proteins involved in chromatin remodeling, ATRX, TOP2B and BAZ2B and validated their interactions by proximity ligation assay and co-immunoprecipitation experiments in GPR88 wild-type and knock-out mice. Consistent with the idea that GPR88 may influence cortical functions, Gpr88 -/- mice exhibit extensive remodeling of retrosplenial, somatosensory and motor cortex networks, and human genetic studies shown association of the Gpr88 gene with bipolar disorders and psychoses. Furthermore, a GPR88 variant was linked to a familial developmental disorder characterized by childhood chorea, learning disabilities and speech retardation. Altogether these data highlight the involvement of GPR88 in cortico-subcortical and intracortical networks function.

Jorge Diaz short biography

– Associate professor at the Faculty of health at the University of Paris since 1991.

– co-leader with Bruno Giros of the team « Pathophysiology of Psychiatric Disorders » of the INCC, CNRS UMR-8002, since 2020.

– 1989.- PhD in Life sciences (speciality cytology) of the University Pierre et Marie Curie – Paris 6.

– 2006.- HDR, speciality Neuroscience of the University Paris Descartes – Paris 5.

Research activity : 63 original publications in peer reviewed journals.

– 1991- 2010, Researcher in the unit Neurobiology and Molecular Pharmacology, INSERM UMRS-109, under the leadership of the Professor Jean-Charles Schwartz. This research unit was then labeled as unit lNSERM UMRS-573 under the leadership of Pierre Sokoloff and Jean-Michel Harrang. In this research units my work was focused on the cellular and regional expression of monoamine receptors in the brain and in particular on the expression and function of the D3 dopamine subtype receptor.

– 2010-2019, Researcher in the Institut de Psychiatrie et Neurosciences de Paris «- INSERM IPNP». In this research center my work was focused on the study of Yif1B, a protein involved in post-golgian vesicular trafficking in neurons of the brain and also in the study of the orphan receptor GPR88 in the rodent Brain.

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