Vertebrate Fidgetin Restrains Axonal Growth by Severing Labile Domains of Microtubules

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

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24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1723-1730
Number of pages8
JournalCell Reports
Volume12
Issue number11
DOIs
Publication statusPublished - Sep 22 2015

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Leo, L., Yu, W., D'Rozario, M., Waddell, E. A., Marenda, D. R., Baird, M. A., ... Baas, P. W. (2015). Vertebrate Fidgetin Restrains Axonal Growth by Severing Labile Domains of Microtubules. Cell Reports, 12(11), 1723-1730. https://doi.org/10.1016/j.celrep.2015.08.017