Vertebrate Fidgetin Restrains Axonal Growth by Severing Labile Domains of Microtubules.
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.
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Lanfranco
L
Leo
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Wenqian
W
Yu
Department of Biology, Drexel University, Philadelphia, PA 19104, USA.
Mitchell
M
D'Rozario
Department of Biology, Drexel University, Philadelphia, PA 19104, USA.
Edward A
EA
Waddell
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Department of Biology, Drexel University, Philadelphia, PA 19104, USA.
Daniel R
DR
Marenda
National High Magnetic Field Laboratory and Department of Biological Science, Florida State University, Tallahassee, FL 32310, USA.
Michelle A
MA
Baird
National High Magnetic Field Laboratory and Department of Biological Science, Florida State University, Tallahassee, FL 32310, USA.
Michael W
MW
Davidson
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Bin
B
Zhou
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Bingro
B
Wu
Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Lisa
L
Baker
Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
David J
DJ
Sharp
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA. Electronic address: pbaas@drexelmed.edu.
Peter W
PW
Baas
D000074183:ATPases Associated with Diverse Cellular Activities; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins; D008870:Microtubules / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D051381:Rats
D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D000074183:ATPases Associated with Diverse Cellular Activities; C519701:Fign protein, Drosophila