Elongator is a microtubule polymerase selective for poly-glutamylated tubulin

Planelles-Herrero, V. J.; Genova, M.; Bittleston, A.; McNally, K. E.; Degliesposti, G.; Magiera, M. M.; Janke, C.; Derivery, E.

doi:10.1101/2023.05.10.540202

bioRxiv · 10.1101/2023.05.10.540202

Elongator is a microtubule polymerase selective for poly-glutamylated tubulin

Planelles-Herrero, V. J.·Genova, M.·Bittleston, A.·McNally, K. E.·Degliesposti, G.·Magiera, M. M.·Janke, C.·Derivery, E.

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Abstract

Elongator is a tRNA-modifying complex that regulates the fidelity of protein translation. Recently, a moonlighting function of Elongator has been identified in regulating polarization of the microtubule cytoskeleton during asymmetric cell division. Elongator induces symmetry breaking of the anaphase midzone by selectively stabilizing microtubules on one side of the spindle. This polarizes the segregation of signalling endosomes containing cell-fate determinants to only one daughter cell, thus contributing to cell fate determination. Here, we unravelled the molecular mechanism by which Elongator controls microtubule dynamics. Elongator binds simultaneously to the tip of microtubules and also to free GTP-tubulin heterodimers via their C-terminal tails. Elongator thereby locally increases tubulin concentration at microtubule ends, which stabilizes microtubules by increasing their growth speed and decreasing their catastrophe rate. We show that the Elp123 and Elp456 subcomplexes bind to microtubules and free tubulin heterodimers, respectively, and that these activities must be coupled for Elongator to stabilize microtubules. Surprisingly, we found that Elp456 has strong selectivity towards polyglutamylated tubulin dimers. Hence, microtubules assembled by Elongator become selectively enriched with polyglutamylated tubulin. Therefore, Elongator can rewrite the tubulin code of growing microtubules, placing it at the core of cytoskeletal dynamics and polarization during asymmetric cell division.

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Planelles-Herrero, V. J., Genova, M., Bittleston, A., McNally, K. E., Degliesposti, G., Magiera, M. M., Janke, C., Derivery, E.. 2023-05-10. Elongator is a microtubule polymerase selective for poly-glutamylated tubulin. https://doi.org/10.1101/2023.05.10.540202

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