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TitleHURP facilitates spindle assembly by stabilizing microtubules and working synergistically with TPX2.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 9689, Year 2024
Publish dateNov 8, 2024
AuthorsVenecia Alexandria Valdez / Meisheng Ma / Bernardo Gouveia / Rui Zhang / Sabine Petry /
PubMed AbstractIn vertebrate spindles, most microtubules are formed via branching microtubule nucleation, whereby microtubules nucleate along the side of pre-existing microtubules. Hepatoma up-regulated protein ...In vertebrate spindles, most 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 γ-TuRC. This function is shifted to promote branching microtubule nucleation through enhanced localization to TPX2 condensates, which form the core of the branch site on microtubules. Lastly, we provide a high-resolution cryo-EM structure of HURP on the microtubule, 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.
External linksNat Commun / PubMed:39516491 / PubMed Central
MethodsEM (single particle)
Resolution2.8 Å
Structure data

47173

9duq

EMDB-47173, PDB-9duq:
HURP(65-174) bound to GMPCPP-stabilized microtubule
Method: EM (single particle) / Resolution: 2.8 Å

Chemicals

ChemComp-G2P:
PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER / GMP-CPP, energy-carrying molecule analogue*YM

ChemComp-MG:
Unknown entry

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM

Source
  • sus scrofa (pig)
  • homo sapiens (human)
KeywordsCELL CYCLE / microtubule / nucleation / spindle / oncogene

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