D1R-Golf signaling modules segregate into compartments

The development of a large signaling model that takes into consideration the existence of at least two D1R-Golf signaling compartments explains the data pattern.

Activation of the protein kinase ERK and the subunit GluR1 of the glutamate-gated AMPAR channels in dendritic spines of D1R+ medium spiny neurons is triggered by dopamine acting via D1R couple to Golf through two different signaling cascades. Curiously, reducing the total amount of D1R affects just the activation of ERK while reduction in Golf only affects the activation of GluR1, a pattern that is incompatible with the principle that a single compartment of D1R-Golf is coupled to both signaling cascades. We have developed a large signaling model that takes into consideration the existence of at least two D1R-Golf signaling compartments, each of them coupled to different signaling cascades. This, together with the assumption of alternate affinities of D1R and Golf for each of the compartments, explains the observed data pattern (Gutierrez-Arenas, Eriksson, & Hellgren Kotaleski, 2014) and these predictions can be easily tested experimentally.

References: 

• Gutierrez-Arenas, O., Eriksson, O., & Hellgren Kotaleski, J. (2014). "Segregation and Crosstalk of D1 Receptor-Mediated Activation of ERK in Striatal Medium Spiny Neurons upon Acute Administration of Psychostimulants." PLoS Computational Biology, 10(1), e1003445. doi:10.1371/journal.pcbi.1003445