Phase separation of TPX2 enhances and spatially coordinates microtubule nucleation
| العنوان: | Phase separation of TPX2 enhances and spatially coordinates microtubule nucleation |
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| المؤلفون: | King, Matthew R., Petry, Sabine |
| المصدر: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020) |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cell biology, Biological reaction, Targeting Protein for Xklp2, Science, General Physics and Astronomy, Cell Cycle Proteins, Spindle Apparatus, Karyopherins, Xenopus Proteins, Branching (polymer chemistry), Biochemistry, Microtubules, Article, General Biochemistry, Genetics and Molecular Biology, Xenopus laevis, 03 medical and health sciences, Cytosol, 0302 clinical medicine, Tubulin, Microtubule, Phase (matter), Animals, lcsh:Science, 030304 developmental biology, Ovum, Microtubule nucleation, 0303 health sciences, Multidisciplinary, biology, Effector, Chemistry, General Chemistry, Meiosis, 030104 developmental biology, biology.protein, Biophysics, lcsh:Q, Microtubule-Associated Proteins, Multipolar spindles, Microtubule-Organizing Center, 030217 neurology & neurosurgery |
| الوصف: | Phase separation of substrates and effectors is proposed to enhance biological reaction rates and efficiency. Targeting protein for Xklp2 (TPX2) is an effector of branching microtubule nucleation in spindles and functions with the substrate tubulin by an unknown mechanism. Here we show that TPX2 phase separates into a co-condensate with tubulin, which mediates microtubule nucleation in vitro and in isolated cytosol. TPX2-tubulin co-condensation preferentially occurs on pre-existing microtubules, the site of branching microtubule nucleation, at the endogenous and physiologically relevant concentration of TPX2. Truncation and chimera versions of TPX2 suggest that TPX2-tubulin co-condensation enhances the efficiency of TPX2-mediated branching microtubule nucleation. Finally, the known inhibitor of TPX2, the importin-α/β heterodimer, regulates TPX2 condensation in vitro and, consequently, branching microtubule nucleation activity in isolated cytosol. Our study demonstrates how regulated phase separation can simultaneously enhance reaction efficiency and spatially coordinate microtubule nucleation, which may facilitate rapid and accurate spindle formation. The microtubule binding protein TPX2 enhances branching microtubule nucleation though the current mechanisms are unclear. Here, the authors show that TPX2 undergoes liquid-liquid phase separation and co-condensates with tubulin to enhance TPX2-mediated microtubule nucleation. |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b5dce3e12ea4f2006f86762bc28bbd9cTest https://doi.org/10.1038/s41467-019-14087-0Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b5dce3e12ea4f2006f86762bc28bbd9c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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