PMID:23373701

Citation	Ahmadiantehrani, S and Ron, D' (2013) Dopamine D2 receptor activation leads to an up-regulation of glial cell line-derived neurotrophic factor via Gβγ-Erk1/2-dependent induction of Zif268. J. Neurochem. '
Abstract	Glial cell line-derived neurotrophic factor (GDNF) is a potent growth factor essential to the development, survival, and function of dopaminergic neurons (Airaksinen and Saarma 2002). The molecular mechanisms underlying GDNF expression remain elusive; thus, we set out to identify a signaling pathway that governs GDNF levels. We found that treatment of both differentiated dopaminergic-like SH-SY5Y cells and rat midbrain slices with the dopamine D2 receptor (D2R) agonist, quinpirole, triggered an increase in the expression of GDNF that was temporally preceded by an increase in the levels of zinc-finger protein 268 (Zif268), a DNA-binding transcription factor encoded by an immediate-early gene. Moreover, the D2R inhibitor raclopride blocked the increase of both GDNF and Zif268 expression following potassium-evoked dopamine release in SH-SY5Y cells. We used adenoviral delivery of small hairpin RNA (shRNA) targeting Zif268 to down-regulate its expression and found that Zif268 is specifically required for the D2R-mediated up-regulation of GDNF. Furthermore, the D2R-mediated induction of GDNF and Zif268 expression was dependent on Gβγ-mediated signaling and activation of extracellular signal-regulated kinase 1/2. Importantly, using chromatin immunoprecipitation assay, we identified a direct association of Zif268 with the GDNF promoter. These results suggest that D2R activation induces a Gβγ- and extracellular signal-regulated kinase 1/2-dependent increase in the level of Zif268, which functions to directly up-regulate the expression of GDNF.
Links	PubMed Online version:10.1111/jnc.12178
Keywords
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:DRD2	involved_in	GO:1900168: positive regulation of glial cell-derived neurotrophic factor secretion	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:DRD2		GO:1900168: positive regulation of glial cell line-derived neurotrophic factor secretion	ECO:0000314:		P		Data from a chromatin immunoprecipitation assay, tehy identified a direct association of Zif268 with the GDNF promoter, and Figure 1 shows that Dopamine D2 receptor (D2R) activation increases glial cell line–derived neurotrophic factor (GDNF) mRNA and protein levels	complete CACAO 7176

References

See Help:References for how to manage references in GONUTS.