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Article Dans Une Revue (Data Paper) EMBO Journal Année : 2023

Tubulin polyglutamylation differentially regulates microtubule-interacting proteins

Résumé

Tubulin posttranslational modifications have been predicted to control cytoskeletal functions by coordinating the molecular inter- actions 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 selec- tively control microtubule interactions in neurons.
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Dates et versions

hal-04247208 , version 1 (18-10-2023)

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Mariya Genova, Lenka Grycova, Verena Puttrich, Maria M Magiera, Zdenek Lansky, et al.. Tubulin polyglutamylation differentially regulates microtubule-interacting proteins. EMBO Journal, 2023, 42 (5), ⟨10.15252/embj.2022112101⟩. ⟨hal-04247208⟩
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