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bioRxiv · 10.64898/2026.08.11.744142

Safeguarding epithelial junctions by a novel quality control pathway

Tocchini, C.·Angonezi, A. L.·Pulido Barrera, D. C.·Mango, S. E.
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Abstract

Cell junctions establish and maintain epithelial architecture despite fluctuating environmental and developmental conditions. A central question is how cells respond to challenging conditions to preserve junctional integrity. Here, we report the discovery of a previously unrecognized quality control pathway that monitors epithelial junctions (J-QC). We used the (I)Caenorhabditis elegans(/I) epidermis as a model to investigate the DLG-1-AJM-1 complex (DAC), a junctional domain that is critical for embryonic morphogenesis. We identify two mechanisms that sustain junctional integrity: first, localized (I)dlg-1(/I) mRNA ensures appropriate DLG-1 protein levels at the junction; repositioning (I)dlg-1(/I) RNA reduces DLG-1 levels, leading to gaps between epithelial cells. Second, transcription of DAC components responds to perturbations that disrupt the DAC. This response is sequence-independent, distinguishing it from other quality control mechanisms. It is activated by perturbations of the DAC or cytoskeleton and requires the LINC complex component ZYG-12/HOOK1-3 to transduce information about junctional integrity to the nucleus. These findings define a novel junctional QC for epithelial maintenance.

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Tocchini, C., Angonezi, A. L., Pulido Barrera, D. C., Mango, S. E.. 2026-08-11. Safeguarding epithelial junctions by a novel quality control pathway. https://doi.org/10.64898/2026.08.11.744142

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