Table · dataset · 2026
Methyl-HLH-30/TFEB orchestrates holistic intestinal recuperation against bacterial pore-forming toxin intoxication via TTC38 in metazoans
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<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).
Description
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.
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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>
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- DOI doi.org/10.6084/m9.figshare.33872681.v1 ↗
DOI / persistent id · from figshare com
Catalogue records · 1
- OAI-PMH record api.figshare.com/v2/oai?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Af… ↗
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- Microscopy 75%
Provenance · 1 source records, 25 field assertions
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