Dopamine promotes NMDA receptor hypofunction in the retina through D-1 receptor-mediated Csk activation, Src inhibition and decrease of GluN2B phosphorylation

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Socodato, R (Author) Other; Santiago, FN (Author) Other; Portugal, CC (Author) Other; Domith, I (Author) Other; Encarnacao, TG (Author) Other; Loiola, EC (Author) Other; Ventura, ALM (Author) Other; Cossenza, M (Author) Other; Relvas, JB (Author) ICBAS; Castro, NG (Author) Other; Paes de Carvalho, R (Author) Other

Journal

Title: Scientific Reports

Vol. 7

ISSN: 2045-2322

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 9 Citations

Scopus - 15 Citations

Other information

Authenticus ID: P-00M-CK9

DOI: 10.1038/srep40912

Abstract (EN): Dopamine and glutamate are critical neurotransmitters involved in light-induced synaptic activity in the retina. In brain neurons, dopamine D-1 receptors (D(1)Rs) and the cytosolic protein tyrosine kinase Src can, independently, modulate the behavior of NMDA-type glutamate receptors (NMDARs). Here we studied the interplay between D1Rs, Src and NMDARs in retinal neurons. We reveal that dopamine-mediated D1R stimulation provoked NMDAR hypofunction in retinal neurons by attenuating NMDA-gated currents, by preventing NMDA-elicited calcium mobilization and by decreasing the phosphorylation of NMDAR subunit GluN2B. This dopamine effect was dependent on upregulation of the canonical D1R/adenylylcyclase/cAMP/PKA pathway, of PKA-induced activation of C-terminal Src kinase (Csk) and of Src inhibition. Accordingly, knocking down Csk or overexpressing a Csk phosphoresistant Src mutant abrogated the dopamine-induced NMDAR hypofunction. Overall, the interplay between dopamine and NMDAR hypofunction, through the D1R/Csk/Src/GluN2B pathway, might impact on light-regulated synaptic activity in retinal neurons.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14