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

Research output: Contribution to journalArticle

22 Citations (Scopus)

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
StatePublished - Sep 22 2015

Fingerprint

Microtubules
Vertebrates
Neurons
Growth
Microtubule Proteins
Axons
Tubulin
Animals
Knockout Mice
Diptera
Drosophila
Rodentia

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

Vertebrate Fidgetin Restrains Axonal Growth by Severing Labile Domains of Microtubules. / Leo, Lanfranco; Yu, Wenqian; D'Rozario, Mitchell; Waddell, Edward A.; Marenda, Daniel R.; Baird, Michelle A.; Davidson, Michael W.; Zhou, Bin; Wu, Bingruo; Baker, Lisa; Sharp, David J.; Baas, Peter W.

In: Cell Reports, Vol. 12, No. 11, 22.09.2015, p. 1723-1730.

Research output: Contribution to journalArticle

Leo, L, Yu, W, D'Rozario, M, Waddell, EA, Marenda, DR, Baird, MA, Davidson, MW, Zhou, B, Wu, B, Baker, L, Sharp, DJ & Baas, PW 2015, 'Vertebrate Fidgetin Restrains Axonal Growth by Severing Labile Domains of Microtubules', Cell Reports, vol. 12, no. 11, pp. 1723-1730. https://doi.org/10.1016/j.celrep.2015.08.017
Leo L, Yu W, D'Rozario M, Waddell EA, Marenda DR, Baird MA et al. Vertebrate Fidgetin Restrains Axonal Growth by Severing Labile Domains of Microtubules. Cell Reports. 2015 Sep 22;12(11):1723-1730. https://doi.org/10.1016/j.celrep.2015.08.017
Leo, Lanfranco ; Yu, Wenqian ; D'Rozario, Mitchell ; Waddell, Edward A. ; Marenda, Daniel R. ; Baird, Michelle A. ; Davidson, Michael W. ; Zhou, Bin ; Wu, Bingruo ; Baker, Lisa ; Sharp, David J. ; Baas, Peter W. / Vertebrate Fidgetin Restrains Axonal Growth by Severing Labile Domains of Microtubules. In: Cell Reports. 2015 ; Vol. 12, No. 11. pp. 1723-1730.
@article{468db8e29d63435589b9c109c3d3b1a2,
title = "Vertebrate Fidgetin Restrains Axonal Growth by Severing Labile Domains of Microtubules",
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.",
author = "Lanfranco Leo and Wenqian Yu and Mitchell D'Rozario and Waddell, {Edward A.} and Marenda, {Daniel R.} and Baird, {Michelle A.} and Davidson, {Michael W.} and Bin Zhou and Bingruo Wu and Lisa Baker and Sharp, {David J.} and Baas, {Peter W.}",
year = "2015",
month = "9",
day = "22",
doi = "10.1016/j.celrep.2015.08.017",
language = "English (US)",
volume = "12",
pages = "1723--1730",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "11",

}

TY - JOUR

T1 - Vertebrate Fidgetin Restrains Axonal Growth by Severing Labile Domains of Microtubules

AU - Leo, Lanfranco

AU - Yu, Wenqian

AU - D'Rozario, Mitchell

AU - Waddell, Edward A.

AU - Marenda, Daniel R.

AU - Baird, Michelle A.

AU - Davidson, Michael W.

AU - Zhou, Bin

AU - Wu, Bingruo

AU - Baker, Lisa

AU - Sharp, David J.

AU - Baas, Peter W.

PY - 2015/9/22

Y1 - 2015/9/22

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84942821536&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84942821536&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2015.08.017

DO - 10.1016/j.celrep.2015.08.017

M3 - Article

VL - 12

SP - 1723

EP - 1730

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 11

ER -