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CRM-1/DBL-1 protein complex regulates Dopaminergic Neurofunctional Abnormalities in Caenorhabditis elegans caused by ionizing radiation

• 1、School of Radiation Medicine and Protection, Soochow University, Suzhou 215123

Abstract：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.

Keywords： Radiology Cysteine-rich motor neuron protein BMP pathway Dopaminergic