Analysis of the Posttranslational Modification of the Transcription Factor HLH-30 after Pore Forming Toxin Intoxication in C elegans

  • 陳 緯學

Student thesis: Master's Thesis


Pore-forming toxins (PFTs) secreted by bacteria can damage the plasma membrane of their target host cells In order to defend PFT autophagy plays an essential role in controlling the tolarance of host cells According to recent research autophagy in mammals is regulated by the transcription factor EB (TFEB) and the C elegans orthologue HLH-30 is also required for auphagy regulation Our previous study demonstrated that HLH-30 translocates from the cytosol into the nucleus of the intestinal cells of C elegans after Cry5B-PFT intoxication In this study we performed a high-throughput genetic suppressor screen to identify novel signaling pathways that control HLH-30 nuclear localization induced by Cry5B-PFT We found that prmt (protein arginine methyltransferases) RNAi significantly abolished the Cry5B-induced HLH-30 nuclear localization Thus our data suggested that the PRMT protein family may participate in the regulation of HLH-30 to activate autophagy In order to reconfirm whether and which PRMT is involved in HLH-30 nuclear localization we tested RNAi of all five CePRMTs in C elegans in the liquid and agar-based assays Even though there were different efficiency in the inhibiton of nuclear localization all five CePRMTs can regulate HLH-30 nuclearlization Furthermore the phenomena are also comfirmed in the five prmt mutant animals We found that HLH-30 nuclear localization and the expression of LGG-1 a downstream gene of HLH-30 were significantly decreased in the prmt-7 mutant animal Taken all together these results demonstrated that prmt-7 could regulate the activity of HLH-30 by posttranslational modification i e -arginine methylation to control autophagy in response to pore-forming toxin intoxification in C elegans
Date of Award2015 Aug 20
Original languageEnglish
SupervisorChang-Shi Chen (Supervisor)

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