| Abstract |
Graphene oxide (GO) can be potentially used in many medical and industrial fields. Using assay system of Caenorhabditis elegans, we identified the NLG-1/Neuroligin-mediated neuronal signaling dysregulated by GO exposure. In nematodes, GO exposure significantly decreased the expression of NLG-1, a postsynaptic cell adhesion protein. Loss-of-function mutation of nlg-1 gene resulted in a susceptible property of nematodes to GO toxicity. Rescue experiments suggested that NLG-1 could act in AIY interneurons to regulate the response to GO exposure. In the AIY interneurons, PKC-1, a serine/threonine protein kinase C (PKC) protein, was identified as the downstream target for NLG-1 in the regulation of response to GO exposure. LIN-45, a Raf protein in ERK signaling pathway, was further identified as the downstream target for PKC-1 in the regulation of response to GO exposure. Therefore, GO may dysregulate NLG-1-mediated molecular signaling in the interneurons, and a neuronal signaling cascade of NLG-1-PKC-1-LIN-45 was raised to be required for the control of response to GO exposure. More importantly, intestinal RNAi knockdown of daf-16 gene encoding a FOXO transcriptional factor in insulin signaling pathway suppressed the resistant property of nematodes overexpressing NLG-1 to GO toxicity, suggesting the possible link between neuronal NLG-1 signaling and intestinal insulin signaling in the regulation of response to GO exposure.
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