Antidepressant-induced differential ubiquitination of beta-arrestins 1 and 2 in mononuclear leucocytes of patients with depression

作者：Golan Moran; Schreiber Gabriel; Avissar Sofia^*

来源：International Journal of Neuropsychopharmacology, 2013, 16(8): 1745-1754.

DOI：10.1017/S1461145713000291

• Antidepressant
• beta-arrestin
• leucocyte
• signal transduction
• ubiquitination

beta-Arrestins 1 and 2, cytosolic proteins known to mediate receptor desensitization, endocytosis and G protein-independent signalling, are post-translationally modified by ubiquitination regulating their ability to serve as adaptors and scaffolds. beta-Arrestins were suggested to play a role in the pathophysiology of depression and in antidepressant mechanism of action. To determine whether a depressive episode or antidepressant treatment induce significant selective differences in beta-arrestin 1 and 2 levels or their ubiquitination patterns in leucocytes of patients with depression, 46 outpatients diagnosed with a depressive episode were examined before and after 4-wk antidepressant treatment compared with age-and gender-matched control subjects. beta-Arrestin levels were measured by immunoblotting using anti-arrestin antibodies. Ubiquitination of beta-arrestins was measured using anti-ubiquitin antibodies followed by an immunoprecipitation step and immunoblotting using anti-arrestin antibodies. Antidepressants induced selective alterations in leucocyte beta-arrestin 1 and 2 levels and ubiquitination. The levels of beta-arrestin 1 and 2 and their ubiquitinated forms in leucocytes of yet untreated patients with depression were significantly decreased in a symptom severity correlated manner compared to control subjects. Antidepressants normalized beta-arrestin 1 and 2 levels and uncovered novel differences between the two isoforms: (a) while antidepressants normalized ubiquitination of beta-arrestin 1, ubiquination of beta-arrestin 2 was unaffected; (b) while under antidepressants ubiquitination extent of beta-arrestin 1 positively correlated with its level, an inverse picture of negative correlation was found between ubiquitination extent of beta-arrestin 2 and its level. We conclude that antidepressants may serve as a tool to detect functional differences between the two beta-arrestin isoforms and that through these differential effects antidepressants can induce specific alterations in alternative cellular signalling.

• 出版日期2013-9