PT - JOURNAL ARTICLE AU - Yue Qu AU - Ines Hahn AU - Stephen Webb AU - Andreas Prokop TI - Periodic actin structures in neuronal axons are required to maintain microtubules AID - 10.1101/049379 DP - 2016 Jan 01 TA - bioRxiv PG - 049379 4099 - http://biorxiv.org/content/early/2016/04/19/049379.short 4100 - http://biorxiv.org/content/early/2016/04/19/049379.full AB - Axons are cable-like neuronal processes wiring the nervous system. These delicate structures have to be sustained for an organism’s lifetime. Their backbones and life-sustaining transport highways are formed by parallel microtubules bundles, surrounded by recently discovered periodic axonal actin structures (PAAS). Here we demonstrate the first functional role of PAAS. Via super-resolution microscopy we show that PAAS are evolutionarily conserved. Imaging of 11 genetic and 3 drug-based manipulations of actin or actin regulators revealed that these structures are composed of short actin filaments dependent on Adducin, Spectrin, Ena/VASP, Arp2/3 and DAAM. They are required to maintain axonal microtubules through sustained polymerisation, in parallel to independent stabilising mechanisms mediated by microtubule-binding spectraplakin proteins. Removing both stabilisation mechanisms triggers axon degeneration. Our data establish PAAS as functionally relevant, evolutionarily conserved structural components of axons. They provide new conceptual explanations for neural disorders linked to cortical actin regulators and for injury-derived axon degeneration.