PRMT-7/PRMT7 activates HLH-30/TFEB to guard plasma membrane integrity compromised by bacterial pore-forming toxins.
Journal
Autophagy
Journal Volume
20
Journal Issue
6
Start Page
1335
End Page
1358
ISSN
1554-8635
Date Issued
2024-06
Author(s)
Hsieh, Hui-Chen
Huang, I-Hsiang
Chang, Shao-Wen
Chen, Po-Lin
Su, Yu-Cheng
Wang, Shuying
Tsai, Wei-Jiun
Aroian, Raffi V
Chen, Chang-Shi
Abstract
Bacterial pore-forming toxins (PFTs) that disrupt host plasma membrane integrity (PMI) significantly contribute to the virulence of various pathogens. However, how host cells protect PMI in response to PFT perforation remains obscure. Previously, we demonstrated that the HLH-30/TFEB-dependent intrinsic cellular defense (INCED) is elicited by PFT to maintain PMI in intestinal epithelium. Yet, the molecular mechanism for the full activation of HLH-30/TFEB by PFT remains elusive. Here, we reveal that PRMT-7 (protein arginine methyltransferase-7) is indispensable to the nuclear transactivation of HLH-30 elicited by PFTs. We demonstrate that PRMT-7 participates in the methylation of HLH-30 on its RAG complex binding domain to facilitate its nuclear localization and activation. Moreover, we showed that PRMT7 is evolutionarily conserved to regulate TFEB cellular localization and repair plasma damage caused by PFTs in human intestinal cells. Together, our observations not only unveil a novel PRMT-7/PRMT7-dependent post-translational regulation of HLH-30/TFEB but also shed insight on the evolutionarily conserved mechanism of the INCED against PFT in metazoans.
Subjects
Intrinsic cellular defense (INCED)
plasma membrane integrity (PMI)
pore-forming toxin (PFT)
protein arginine methyltransferase-7 (PRMT7/PRMT-7)
transcription factor EB (TFEB/HLH-30)
SDGs
Type
journal article