Vertebrate Fidgetin Restrains Axonal Growth by Severing Labile Domains of Microtubules.

Lanfranco Leo,Michelle A Baird,Bingro Wu,Daniel R Marenda,Mitchell D’Rozario,Peter W Baas,Bin Zhou,David J Sharp,Edward A Waddell,Wenqian Yu,Lisa Baker,Michael W Davidson

doi:10.1016/j.celrep.2015.08.017

Abstract

SUMMARYIndividual microtubules (MTs) in the axon consist of a stable domain that is highly acetylated and a labile domain that is not. Traditional MT-severing proteins preferentially cut the MT in the stable domain. In Drosophila, fidgetin behaves in this fashion, with targeted knockdown resulting in neurons with a higher fraction of acetylated (stable) MT mass in their axons. Conversely, in a fidgetin knockout mouse, the fraction of MT mass that is acetylated is lower than in the control animal. When fidgetin is depleted from cultured rodent neurons, there is a 62% increase in axonal MT mass, all of which is labile. Concomitantly, there are more minor processes and a longer axon. Together with experimental data showing that vertebrate fidgetin targets unacetylated tubulin, these results indicate that vertebrate fidgetin (unlike its fly ortholog) regulates neuronal development by tamping back the expansion of the labile domains of MTs.

Highlights

In the axon, each microtubule (MT) consists of a stable domain from which can elongate a labile domain (Baas and Black, 1990)
The stable and labile domains are situated toward the minus and plus ends of the MT, respectively, with the labile portion of the MT directed toward the tip of the axon
Results of our study indicate that vertebrate Fgn regulates neuronal development by targeting labile domains of MTs

Summary

Introduction

Each microtubule (MT) consists of a stable domain from which can elongate a labile domain (Baas and Black, 1990). If the breakage occurs in the stable domain of an MT, the result is two new MTs, both capable of growing longer. This allows for an increase in MT number, locally within the axon, for example, at sites of branch formation (Qiang et al, 2010). If this breakage were to occur in a labile domain, the expected result would be just one MT that is shorter than the original, as an MT with no stable domain would depolymerize completely.

Results

Discussion

Conclusion