Microtubules (MTs) are crucial for regeneration in the peripheral nervous system (PNS), providing structural support to healing axons and routes for intracellular transport. The stathmin family protein SCG10 regulates MT dynamics by sequestering unpolymerized tubulin dimers and promoting local MT assembly. SCG10 is important for axon maintenance and regeneration, suggesting that it regulates MT stability during growth and repair in both the central nervous system and PNS. In this study (Li et al., 2023), Jianguo Chen and colleagues generate a Scg10 knockout mouse model to demonstrate a link between MT stability and axon homeostasis in the PNS. Adult Scg10−/− mice develop motor dysfunction associated with neuromuscular junction denervation and impaired axon regeneration, with fewer MTs found in motor axons with smaller diameters. Furthermore, loss of SCG10 in cultured dorsal root ganglion (DRG) neurons promotes tubulin acetylation, which stabilises MTs. However, transport of mitochondria and lysosomes along MTs is slowed and axon outgrowth is impaired in the absence of SCG10. Lastly, the authors confirm previous observations that phospho-regulation of the MT depolymerising activity of SCG10 plays a role in axon outgrowth as a phosphomimetic SCG10 mutant failed to rescue Scg10−/− phenotypes in cultured DRG neurons. These findings suggest that over-stabilisation of MTs associated with a dysregulation of factors such as SCG10 can be detrimental to long-term homeostasis in the PNS.
