| First Author | Park SK | Year | 2005 |
| Journal | Cell | Volume | 122 |
| Issue | 2 | Pages | 275-87 |
| PubMed ID | 16051151 | Mgi Jnum | J:115199 |
| Mgi Id | MGI:3690835 | Doi | 10.1016/j.cell.2005.05.031 |
| Citation | Park SK, et al. (2005) Par-4 links dopamine signaling and depression. Cell 122(2):275-87 |
| abstractText | Prostate apoptosis response 4 (Par-4) is a leucine zipper containing protein that plays a role in apoptosis. Although Par-4 is expressed in neurons, its physiological role in the nervous system is unknown. Here we identify Par-4 as a regulatory component in dopamine signaling. Par-4 directly interacts with the dopamine D2 receptor (D2DR) via the calmodulin binding motif in the third cytoplasmic loop. Calmodulin can effectively compete with Par-4 binding in a Ca2+-dependent manner, providing a route for Ca2+-mediated downregulation of D2DR efficacy. To examine the importance of the Par-4/D2DR interaction in dopamine signaling in vivo, we used a mutant mouse lacking the D2DR interaction domain of Par-4, Par-4DeltaLZ. Primary neurons from Par-4DeltaLZ embryos exhibit an enhanced dopamine-cAMP-CREB signaling pathway, indicating an impairment in dopamine signaling in these cells. Remarkably, Par-4DeltaLZ mice display significantly increased depression-like behaviors. Collectively, these results provide evidence that Par-4 constitutes a molecular link between impaired dopamine signaling and depression. |
