Tubulin polyglutamylation differentially regulates microtubule-interacting proteins

0570212 - BTÚ 2024 RIV GB eng J - Journal Article
Genova, M. - Gryčová, Lenka - Puttrich, Verena - Magiera, M. M. - Lánský, Zdeněk - Janke, C. - Braun, Marcus
Tubulin polyglutamylation differentially regulates microtubule-interacting proteins.
EMBO Journal. Roč. 42, č. 5 (2023). ISSN 0261-4189. E-ISSN 1460-2075
R&D Projects: GA ČR(CZ) GX19-27477X; GA ČR(CZ) GA22-11753S; GA MŠMT(CZ) LM2015043; GA MŠMT(CZ) LM2018129; GA MŠMT(CZ) EF16_013/0001775
Institutional support: RVO:86652036
Keywords : katanin * kinesin-1 * microtubule-associated Tau * microtubules * polyglutamylation * tubulin posttranslational modifications
OECD category: Biochemistry and molecular biology
Impact factor: 11.4, year: 2022
Method of publishing: Open access
https://www.embopress.org/doi/full/10.15252/embj.2022112101

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.
Permanent Link: https://hdl.handle.net/11104/0342621