RM-1/DBL-1蛋白复合物调节电离辐射诱导的秀丽隐杆线虫多巴胺能神经功能异常

Objective: To investigate the molecular mechanisms underlying ionizing radiation (IR)-induced dopaminergic neuronal dysfunction in Caenorhabditis elegans (C. elegans).Methods: crm-1 and dbl-1 were knocked down or knocked out using CRISPR/Cas9, RNA interference (RNAi), and mutant strains. The roles of CRM-1 and DBL-1 in IR-induced dopaminergic dysfunction were further examined using HADDOCK molecular docking simulations.Results: Ionizing radiation induced dopaminergic neuronal dysfunction and downregulated expression of the dopamine transporter DAT-1 in C. elegans, concomitant with upregulated expression of both crm-1 gene and CRM-1 protein. Knockout or knockdown of crm-1 ameliorated the IR-induced dopaminergic dysfunction and elevated DAT-1 protein expression. Loss-of-function mutation (dbl-1 null) or RNAi-mediated knockdown of dbl-1 resulted in increased DAT-1 protein expression.Conclusion: CRM-1 and DBL-1 co-regulate the dopaminergic neuronal dysfunction induced by ionizing radiation in Caenorhabditis elegans.