Ctr9, a Protein in the Transcription Complex Paf1, Regulates Dopamine Transporter Activity at the Plasma Membrane

Abstract

Background:The dopamine transporter controls the concentration of dopamine at the synapse. Results: Ctr9, formerly identified as a nuclei protein, interacts with the dopamine transporter in the cytoplasmic compartment. Conclusion: This interaction facilitates the targeting of the dopamine transporter to the plasma membrane and increases its activity. Significance: Identifying the complete dopamine transporter interactome is essential to understanding how neurotransmission is regulated.

Structural and Functional Characterization of the Interaction of Snapin with the Dopamine Transporter: Differential Modulation of Psychostimulant Actions

“…We investigated whether DAT and snapin transcripts are coexpressed in neurons using double-labeling fluorescent insitu hybridization (FISH). As previously described (De Gois et al, 2015;Giros et al, 1991), DAT expression is restricted to the SNc and the ventral tegmental area (VTA), whereas snapin expression profile is more ubiquitous (Figure 2a and Supplementary Figure S2a). At high magnification, we observed that snapin and DAT transcripts are coexpressed in neurons of the SNc and VTA (Figure 2a).…”

“…This suggests that mutants that cannot bind snapin are not correctly exported to the membrane, again reinforcing the hypothesis that snapin has a role in DAT trafficking. Other studies identifying the molecular determinants regulating transporter trafficking and interactions with other proteins have focused on domains in DAT-CT others than the one identified in our study: the PDZ domain (Rickhag et al, 2013;Torres et al, 2001), residues 612-617 flanking the PDZ domain (Bjerggaard et al, 2004;Fog et al, 2006), and the initial residues before C580 (Carneiro et al, 2002;De Gois et al, 2015).…”

“…Yeast Two-Hybrid Y2H screening was performed by Hybrigenics (France) and experiments were performed as previously described (De Gois et al, 2015).…”

“…Uptake were performed as described (De Gois et al, 2015) with some modifications. A MultiScreen HTS vacuum manifold with 96-well plates (Merck Millipore) were used with 10-15 μg of striatal synaptosomes.…”

Regulation of Hematopoietic Activity Involving New Interacting Partners (RRAGC & PSMC2, CKAP4 & MANF and CTR9 & CNTNAP2)

“…The role of the SH2 domain of CTR9 in nuclear localization has also been demonstrated, which confirms that CTR9 localization is not restricted to the nucleus, as its function has been primarily illustrated in the transcription complex Paf1. Thus, the recent research indicates that CTR9 modulates DAT function by regulating its trafficking [29].…”