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

## TL;DR

This study reveals how the protein MIG-6/papilin helps maintain the structure of neurons over a lifetime by remodeling collagen in the brain's extracellular matrix.

## Contribution

The study identifies MIG-6/papilin as a novel regulator of neuronal architecture through extracellular matrix remodeling.

## Key findings

- MIG-6/papilin remodels collagen IV in the extracellular matrix to maintain neuronal stability.
- Collaboration with MIG-17/ADAMTS and PXN-2/peroxidasin is essential for this remodeling process.
- The mechanism supports neuronal architecture under mechanical stress and over time.

## 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.