Remodeling of extracellular matrix collagen IV by MIG-6/papilin regulates neuronal architecture

Nadour, M.; LEATIS, R. I. V. R.; BIARD, M.; FREBAULT, N.; RIVOLLET, L.; St-Louis, P.; Blanchette, C. R.; Thackeray, A.; PERRAT, P.; BEVILACQUA, C.; PREVEDEL, R.; CAPPADOCIA, L.; Rapti, G.; Doitsidou, M.; Benard, C. Y.

doi:10.1101/2025.02.10.637428

bioRxiv · 10.1101/2025.02.10.637428

Remodeling of extracellular matrix collagen IV by MIG-6/papilin regulates neuronal architecture

Nadour, M.·LEATIS, R. I. V. R.·BIARD, M.·FREBAULT, N.·RIVOLLET, L.·St-Louis, P.·Blanchette, C. R.·Thackeray, A.·PERRAT, P.·BEVILACQUA, C.·PREVEDEL, R.·CAPPADOCIA, L.·Rapti, G.·Doitsidou, M.·Benard, C. Y.

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Abstract

Neuronal architecture established embryonically must persist lifelong to ensure normal brain function. However, little is understood about the mechanisms behind the long-term maintenance of neuronal organization. To uncover maintenance mechanisms, we performed a suppressor screen in sax-7/L1CAM mutants, which exhibit progressive disorganization with age. We identified the conserved extracellular matrix protein MIG-6/papilin as a key regulator of neuronal maintenance. Combining incisive molecular genetics, structural predictions, in vivo quantitative imaging, and cutting-edge Brillouin microscopy, we show that MIG-6/papilin remodels extracellular matrix collagen IV, working in concert with the secreted enzymes MIG-17/ADAMTS and PXN-2/peroxidasin. This remodeling impacts tissue biomechanics and ensures neuronal stability, even under increased mechanical stress. Our findings highlight an extracellular mechanism by which MIG-6/papilin supports the integrity of neuronal architecture throughout life. This work provides critical insights into the molecular basis of sustaining neuronal architecture and offers a foundation for understanding age-related and neurodegenerative disorders.

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Nadour, M., LEATIS, R. I. V. R., BIARD, M., FREBAULT, N., RIVOLLET, L., St-Louis, P., Blanchette, C. R., Thackeray, A., PERRAT, P., BEVILACQUA, C., PREVEDEL, R., CAPPADOCIA, L., Rapti, G., Doitsidou, M., Benard, C. Y.. 2025-02-10. Remodeling of extracellular matrix collagen IV by MIG-6/papilin regulates neuronal architecture. https://doi.org/10.1101/2025.02.10.637428

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