Par-4 links dopamine signaling and depression
SCIE
SCOPUS
- Title
- Par-4 links dopamine signaling and depression
- Authors
- Park, SK; Nguyen, MD; Fischer, A; Luke, MPS; Affar, EB; Dieffenbach, PB; Tseng, HC; Shi, Y; Tsai, LH
- Date Issued
- 2005-07-29
- Publisher
- CELL PRESS
- Abstract
- 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-4 Delta LZ Primary neurons from Par-4 Delta LZ embryos exhibit an enhanced dopamine-cAMP-CREB signaling pathway, indicating an impairment in dopamine signaling in these cells. Remarkably, Par-4 Delta LZ 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.
- Keywords
- PROSTATE APOPTOSIS RESPONSE-4; ELEMENT-BINDING PROTEIN; NUCLEUS-ACCUMBENS; NEURONAL DEGENERATION; HUNTINGTONS-DISEASE; AFFECTIVE-DISORDERS; MAJOR DEPRESSION; MOUSE MODEL; RECEPTOR; ANTIDEPRESSANT
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/28378
- DOI
- 10.1016/j.cell.2005.05.031
- ISSN
- 0092-8674
- Article Type
- Article
- Citation
- CELL, vol. 122, no. 2, page. 275 - 287, 2005-07-29
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- There are no files associated with this item.
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