HURP facilitates spindle assembly by stabilizing microtubules and working synergistically with TPX2

Valdez, V. A.; Ma, M.; Gouveia, B.; Zhang, R.; Petry, S.

doi:10.1101/2023.12.18.571906

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bioRxiv · 10.1101/2023.12.18.571906

HURP facilitates spindle assembly by stabilizing microtubules and working synergistically with TPX2

Valdez, V. A.·Ma, M.·Gouveia, B.·Zhang, R.·Petry, S.

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Abstract

In large vertebrate spindles, the majority of microtubules are formed via branching microtubule nucleation, whereby microtubules nucleate along the side of pre-existing microtubules. Hepatoma up-regulated protein (HURP) is a microtubule-associated protein that has been implicated in spindle assembly, but its mode of action is yet to be defined. In this study, we show that HURP is necessary for RanGTP-induced branching microtubule nucleation in Xenopus egg extract. Specifically, HURP stabilizes the microtubule lattice to promote microtubule formation from {gamma}- TuRC. This function is shifted to promote branching microtubule nucleation in the presence of TPX2, another branching-promoting factor, as HURPs localization to microtubules is enhanced by TPX2 condensation. Lastly, we provide a structure of HURP on the microtubule lattice, revealing how HURP binding stabilizes the microtubule lattice. We propose a model in which HURP stabilizes microtubules during their formation, and TPX2 preferentially enriches HURP to microtubules to promote branching microtubule nucleation and thus spindle assembly.

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Valdez, V. A., Ma, M., Gouveia, B., Zhang, R., Petry, S.. 2023-12-18. HURP facilitates spindle assembly by stabilizing microtubules and working synergistically with TPX2. https://doi.org/10.1101/2023.12.18.571906

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