TY - JOUR T1 - Changes in neuronal immunofluorescence in the C- versus N-terminal domains of hnRNP H following D1 dopamine receptor activation JF - bioRxiv DO - 10.1101/305565 SP - 305565 AU - Qiu T. Ruan AU - Neema Yazdani AU - Jacob A. Beierle AU - Kathryn M. Hixson AU - Kristen E. Hokenson AU - Daniel J. Apicco AU - Kimberly P. Luttik AU - Karen Zheng AU - Peter E. A. Ash AU - Karen K. Szumlinski AU - Shelley J. Russek AU - Benjamin Wolozin AU - Camron D. Bryant Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/04/20/305565.abstract N2 - RNA binding proteins are a diverse class of proteins that regulate all aspects of RNA metabolism. Accumulating studies indicate that heterogeneous nuclear ribonucleoproteins are associated with cellular adaptations in response to drugs of abuse. We recently mapped and directly validated heterogeneous nuclear ribonucleoprotein H1 (Hnrnph1) as a quantitative trait gene underlying differential behavioral sensitivity to methamphetamine. The molecular mechanisms by which hnRNP H1 alters methamphetamine behavior are unknown but could involve pre - and/or post-synaptic changes in protein localization and function. Methamphetamine initiates post-synaptic D1 dopamine receptor signaling indirectly by binding to pre-synaptic dopamine transporters and vesicular monoamine transporters of midbrain dopaminergic neurons which triggers reverse transport and accumulation of dopamine at the synapse. Here, we examined changes in neuronal localization of hnRNP H in primary rat cortical neurons that express dopamine receptors that can be activated by the D1 or D2 dopamine receptor agonists SKF38393 and (-)-Quinpirole HCl, respectively. Basal immunostaining of hnRNP H was localized primarily to the nucleus. D1 dopamine receptor activation induced an increase in hnRNP H nuclear immunostaining as detected by immunocytochemistry with a C-domain directed antibody (epitope near the glycine-rich domain) but not with an N-domain specific antibody. Although there was no change in hnRNP H protein in the nucleus or cytoplasm, there was a decrease in Hnrnph1 transcript following D1 receptor stimulation. Taken together, these results suggest that D1 receptor activation increases availability of the hnRNP H C-terminal epitope, which could potentially reflect changes in protein-protein interactions. Thus, D1 receptor signaling could represent a key molecular post-synaptic event linking Hnrnph1 polymorphisms to drug-induced behavior.HighlightsWe investigated immunofluorescence and localization of hnRNP H following dopamine receptor activation in primary rat cortical neurons.Activation of D1 dopamine receptor increased nuclear immunofluorescence of C-terminal but not the N-terminal domain of hnRNP H with no change in either nuclear or cytoplasmic levels of hnRNP H protein.D1 dopamine signaling could alter interaction of hnRNP H with other proteins. ER -