Motor-dependent microtubule disassembly driven by tubulin tyrosination.
In cells, stable microtubules (MTs) are covalently modified by a carboxypeptidase, which removes the C-terminal Tyr residue of alpha-tubulin. The significance of this selective detyrosination of MTs is not understood. In this study, we report that tubulin detyrosination in fibroblasts inhibits MT disassembly. This inhibition is relieved by overexpression of the depolymerizing motor mitotic centromere-associated kinesin (MCAK). Conversely, suppression of MCAK expression prevents disassembly of normal tyrosinated MTs in fibroblasts. Detyrosination of MTs suppresses the activity of MCAK in vitro, apparently as the result of a decreased affinity of the adenosine diphosphate (ADP)-inorganic phosphate- and ADP-bound forms of MCAK for the MT lattice. Detyrosination also impairs MT disassembly in neurons and inhibits the activity of the neuronal depolymerizing motor KIF2A in vitro. These results indicate that MT depolymerizing motors are directly inhibited by the detyrosination of tubulin, resulting in the stabilization of cellular MTs. Detyrosination of transiently stabilized MTs may give rise to persistent subpopulations of disassembly-resistant polymers to sustain subcellular cytoskeletal differentiation.
Peris
Leticia
L
Institut National de la Santé et de la Recherche Medicale Unité 836, Institut des Neurosciences de Grenoble, 38042 Grenoble, Cedex 9, France. Leticia.peris@ujf-grenoble.fr
Wagenbach
Michael
M
Lafanechère
Laurence
L
Brocard
Jacques
J
Moore
Ayana T
AT
Kozielski
Frank
F
Job
Didier
D
Wordeman
Linda
L
Andrieux
Annie
A
D000818:Animals; D048430:Cell Shape; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism*; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D015739:Nocodazole / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
D020409:Molecular Motor Proteins; D011993:Recombinant Fusion Proteins; D014404:Tubulin; D050257:Tubulin Modulators; D014443:Tyrosine; D016547:Kinesins; D015739:Nocodazole