Tubulin polyglutamylation differentially regulates microtubule‐interacting proteins

Abstract: Tubulin posttranslational modifications have been predicted to control cytoskeletal functions by coordinating the molecular interactions between microtubules and their associating proteins. A prominent tubulin modification in neurons is polyglutamylation, the deregulation of which causes neurodegeneration. Yet, the underlying molecular mechanisms have remained elusive. Here, using in‐vitro reconstitution, we determine how polyglutamylation generated by the two predominant neuronal polyglutamylases, TTLL1 and TTLL7, specifically modulates the activities of three major microtubule interactors: the microtubule‐associated protein Tau, the microtubule‐severing enzyme katanin and the molecular motor kinesin‐1. We demonstrate that the unique modification patterns generated by TTLL1 and TTLL7 differentially impact those three effector proteins, thus allowing for their selective regulation. Given that our experiments were performed with brain tubulin from mouse models in which physiological levels and patterns of polyglutamylation were altered by the genetic knockout of the main modifying enzymes, our quantitative measurements provide direct mechanistic insight into how polyglutamylation could selectively control microtubule interactions in neurons.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Tubulin polyglutamylation differentially regulates microtubule‐interacting proteins ; day:13 ; month:01 ; year:2023 ; extent:22
The EMBO journal / European Molecular Biology Organization ; (13.01.2023) (gesamt 22)

Creator
Genova, Mariya
Grycova, Lenka
Puttrich, Verena
Magiera, Maria M.
Lansky, Zdenek
Janke, Carsten
Braun, Marcus

DOI
10.15252/embj.2022112101
URN
urn:nbn:de:101:1-2023011314282437651405
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
28.07.0008, 12:28 PM CET

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Associated

  • Genova, Mariya
  • Grycova, Lenka
  • Puttrich, Verena
  • Magiera, Maria M.
  • Lansky, Zdenek
  • Janke, Carsten
  • Braun, Marcus

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