Coupling of tubulin acetylation to microtubule stabilization through molecular mimicry

Perez-Bertoldi, J. M.; Dang, T. m. J.; Golcuk, M.; Lanska, E.; Lopes, D.; Henriot, V.; Luo, J.; Zhang, R.; Ti, S.-C.; Janke, C.; Lansky, Z.; Gur, M.; Del Bene, F.; Nogales, E.

doi:10.64898/2026.07.08.736797

bioRxiv · 10.64898/2026.07.08.736797

Coupling of tubulin acetylation to microtubule stabilization through molecular mimicry

Perez-Bertoldi, J. M.·Dang, T. m. J.·Golcuk, M.·Lanska, E.·Lopes, D.·Henriot, V.·Luo, J.·Zhang, R.·Ti, S.-C.·Janke, C.·Lansky, Z.·Gur, M.·Del Bene, F.·Nogales, E.

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Abstract

Microtubules support diverse cellular functions through regulation by microtubule-associated proteins and tubulin post-translational modification, yet how these two layers are mechanistically integrated remains unclear. -tubulin acetylation marks mechanically resilient microtubules, and its incorporation in defined microtubule sub-populations is not well understood. Here, we identify MTCL1 as a molecular link between microtubule stabilization and post-translational modification installation. We find that MTCL1 stabilizes microtubules and alters the luminal surface when copolymerized with tubulin, remodeling -tubulin and enhancing TAT-mediated tubulin acetylation through molecular mimicry. This effect depends on assembly history and is not observed in pre-assembled microtubules. Targeted deletion of MTCL1 in zebrafish impacts axonal organization, leading to motor defects and increased seizure susceptibility. These findings establish MTCL1 as a licensing factor that couples microtubule stabilization with acetylation to regulate neuronal function.

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Perez-Bertoldi, J. M., Dang, T. m. J., Golcuk, M., Lanska, E., Lopes, D., Henriot, V., Luo, J., Zhang, R., Ti, S.-C., Janke, C., Lansky, Z., Gur, M., Del Bene, F., Nogales, E.. 2026-07-09. Coupling of tubulin acetylation to microtubule stabilization through molecular mimicry. https://doi.org/10.64898/2026.07.08.736797

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