2026-10-14T06:10:58Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33872681 2026-09-17T07:00:05Z category_1 category_4 category_8 category_12 category_13 category_14 category_16 category_873 category_106 category_46 category_61 category_132 category_134 portal_87 item_type_3 month_year_09_2026

Methyl-HLH-30/TFEB orchestrates holistic intestinal recuperation against bacterial pore-forming toxin intoxication via TTC38 in metazoans Hui-Chen Hsieh (17833960) Yi-Lin Cheng (355055) Chyuan-Chuan Wu (25002539) Chee Kit Joshua Luk (25002542) Yi-Hsiu Weng (25002545) Tzu-Hsuan Chiu (11212970) Shao-Wen Chang (17833966) Ting-Wei Chang (3211284) Yan-Ning Gu (25002548) Jhen-Wei Ruan (3357539) Tzer-Min Lee (25002551) Shuying Wang (150543) Po-Lin Chen (300281) Raffi V. Aroian (103098) Chang-Shi Chen (256170) Biophysics Biochemistry Microbiology Cell Biology Genetics Molecular Biology Physiology Chemical Sciences not elsewhere classified Science Policy Immunology Developmental Biology Infectious Diseases Virology Bacterial pore-forming toxins (PFTs) effector-triggered immunity (ETI) guard system intrinsic cellular defense (INCED) plasma membrane integrity (PMI) transcription factor EB (TFEB/HLH-30) <p>Effector-triggered immunity (ETI) safeguards intestinal epithelial cells (IECs) by surveilling bacterial virulence effectors or the damage they cause, such as pore-forming toxins (PFTs) that breach plasma membrane integrity (PMI). However, how metazoan ETI regulators guard IEC homeostasis compromised by PFT <i>in vivo</i> remains elusive. Moreover, while the molecular architectures of ETI are well-defined in plants, functionally analogous systems in animals are only beginning to emerge. Here, we unveil a conserved ETI guard system – the intestinal ETI regulator methyl-HLH-30/TFEB upregulates a novel intrinsic cellular defense (INCED) orchestrator Y54G11A.4/TTC38 – in <i>Caenorhabditis elegans</i> and human IECs. This conserved ETI system coordinates the restoration of PMI, microvilli architecture, and nutrient absorption concurrently by promoting phase condensation of the PTRN-1/CAMSAP-dependent guard program through an HSPA/HSP70-HSP90 chaperone system. Together, our findings reveal an intestinal ETI guard system that couples PFT-damage sensing to comprehensive epithelial recuperation, underscoring its physiological relevance for mucosal homeostasis across metazoans.</p> <p><b>Abbreviations and acronyms</b><i>B. thuringiensis</i> (Bt): <i>Bacillus thuringiensis</i>; CAMSAP: calmodulin regulated spectrin associated protein; <i>C. elegans</i>: <i>Caenorhabditis elegans</i>; Cry toxins: crystal toxins; ETI: effector-triggered immunity; FRAP: fluorescence recovery after photobleaching; FRET: Förster/fluorescence resonance energy transfer; GFP: green fluorescent protein; <i>hlh</i>/HLH: helix loop helix; HSP: heat shock protein; IDRs: intrinsically disordered regions; IECs: intestinal epithelial cells; INCED: intrinsic cellular defense; IPTG: isopropyl-β-D-1-thiogalactopyranoside; <i>lgg</i>/LGG: LC3 and GABARAP family; ncMTOC: non-centrosomal microtubule-organizing center; LLPS: liquid-liquid phase separation; PFTs: pore-forming toxins; PI: propidium iodide; PMI: plasma membrane integrity; PTMs: post-translational modifications; qRT-PCR: quantitative real-time PCR; RNAi: ribonucleic acid interference; SEM: scanning electron microscopy; SLO: streptolysin O; SQST-1/SQSTM1/p62: sequestosome related 1; TFEB: transcription factor EB; TPR: tetratricopeptide repeat motifs; TTC38: tetratricopeptide repeat domain 38</p> 2026-09-17T07:00:05Z Dataset Dataset 10.6084/m9.figshare.33872681.v1 https://figshare.com/articles/dataset/Methyl-HLH-30_TFEB_orchestrates_holistic_intestinal_recuperation_against_bacterial_pore-forming_toxin_intoxication_via_TTC38_in_metazoans/33872681 CC BY 4.0