Differential expression of Cul4a and Cul4b by NMDA-evoked neuronal activity

Abstract

Cul4a and Cul4b are a core component of cullin-RING-based E3 ubiquitin ligase complex, which has multiple functions including DNA repair, chromatin remodeling and cell cycle regulation via ubiquitination of Ddb1-recruited target molecules. Although they have highly overlapped functions with high homology on their protein sequences as paralogue proteins, an irreplaceable role among them has been also proposed. Especially, Cul4b plays a critical role in neurodevelopment implicated with X-linked mental retardation unlike Cul4a. However, a specific role of CUL4A in nervous system has been veiled. In this study, we found that proteins of Cul4a and Cul4b are enriched in differential intracellular compartment of neurons. In addition, glutamate-evoked neuronal activity induces nuclear translocation of Cul4a with degradation of Cul4b. Pharmacological study shows that this process is mediated by intracellular calcium influx via NMDA receptor. Taken together, we suggest that Cul4a has an irreplaceable and differential role in nervous system compared to Cul4b.