Vertebrate Fidgetin Restrains Axonal Growth by Severing Labile Domains of Microtubules

Cell Reports
Lanfranco LeoPeter W Baas

Abstract

Individual 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.

References

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Citations

Mar 6, 2016·Current Opinion in Neurobiology·Sam Fb van Beuningen, Casper C Hoogenraad
Apr 21, 2016·Cell Cycle·Caroline DelandreAdrian W Moore
May 29, 2016·Trends in Neurosciences·Olga I Kahn, Peter W Baas
Oct 26, 2016·Brain Research Bulletin·Andrew J Matamoros, Peter W Baas
Jul 8, 2016·Cell Cycle·Xiaoyu ZhaoChunguang Wang
Feb 19, 2016·Cytoskeleton·Peter W BaasLanfranco Leo
Oct 27, 2017·International Journal of Molecular Sciences·Dorota WlogaHanna Fabczak
Sep 8, 2017·The Journal of Cell Biology·Xiaoyi QuFrancesca Bartolini
Oct 31, 2018·The Journal of Cell Biology·Francis J McNally, Antonina Roll-Mecak
Apr 16, 2020·Developmental Neurobiology·Melissa M RollsChengye Feng
Jul 3, 2018·Frontiers in Cellular Neuroscience·Micaela LasserLaura Anne Lowery
Mar 15, 2018·The Journal of Cell Biology·Coralie FassierJamilé Hazan
Feb 16, 2021·Frontiers in Cell and Developmental Biology·Zhangji DongMei Liu
Apr 2, 2019·Trends in Cell Biology·Peter W Baas, Liang Qiang
May 17, 2021·Biochemical and Biophysical Research Communications·Ayaka HagitaTomohiro Miyasaka

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Methods Mentioned

BETA
acetylation
Transgenic

Software Mentioned

Axiovision
Excel
SPSS

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