# Golgi-mediated microtubule nucleation is associated with initiation of vertebrate peripheral neuron regeneration

## TL;DR

This study reveals that the Golgi apparatus plays a key role in triggering regeneration of peripheral neurons after injury, offering new insights for potential therapies.

## Contribution

The study identifies Golgi-mediated microtubule nucleation as a conserved mechanism initiating peripheral neuron regeneration.

## Key findings

- Golgi fragmentation followed by re-compaction is a prerequisite for regeneration.
- AKAP9 and γ-tubulin recruitment leads to microtubule nucleation from the Golgi.
- Disruption of Golgi compaction or AKAP9 recruitment inhibits regeneration.

## Abstract

Peripheral neurons have the potential to regenerate following injury, yet a poor understanding of the cell intrinsic drivers of this process have prevented clinical exploitation. Using in vitro and in vivo models, we define a conserved mechanistic basis for initiation of adult human and rat peripheral neuron regeneration that highlights the Golgi as a major driver of peripheral neuron regeneration. Acute injury first induces somatic Golgi fragmentation followed by rapid re-compaction as a pre-requisite to regeneration. Initiation of axon regeneration is then triggered through transient stepwise recruitment of the microtubule nucleation factors AKAP9 and γ-tubulin, resulting in Golgi-mediated microtubule nucleation. Consequently, disruption of Golgi compaction or AKAP9 and γ-tubulin recruitment compromises induction of microtubule nucleation and initiation of regeneration. This work redefines our understanding of the conserved cell-intrinsic mechanisms initiating peripheral neuron regeneration and identifies Golgi-mediated microtubule nucleation as a key therapeutic target in an area of clinical unmet need.

•Peripheral neuron injury induces Golgi fragmentation followed by re-compaction•AKAP9 and γ-tubulin recruitment leads to Golgi-mediated microtubule nucleation•Inhibition of Golgi compaction or recruitment of AKAP9 inhibits axon regeneration•These mechanisms are conserved between rat and human species

Peripheral neuron injury induces Golgi fragmentation followed by re-compaction

AKAP9 and γ-tubulin recruitment leads to Golgi-mediated microtubule nucleation

Inhibition of Golgi compaction or recruitment of AKAP9 inhibits axon regeneration

These mechanisms are conserved between rat and human species

Molecular biology; Neuroscience; Cell biology.