The Aurora-A/TPX2 Axis Directs Spindle Orientation in Adherent Human Cells by Regulating NuMA and Microtubule Stability
| Autor: | Francesco D. Naso, Italia Anna Asteriti, Giulia Guarguaglini, Alessandro Rosa, Davide Valente, Valentina Palmerini, Marina Mapelli, Divya Singh, Alexander W. Bird, Federica Polverino |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cell division Targeting Protein for Xklp2 Dynein Mitosis Cell Cycle Proteins macromolecular substances Spindle Apparatus Biology Microtubules General Biochemistry Genetics and Molecular Biology Spindle pole body 03 medical and health sciences 0302 clinical medicine Aurora-A/TPX2 complex NuMA cell cortex cell division microtubules mitosis spindle orientation spindle poles Microtubule Cell cortex Humans Metaphase Dyneins Cell biology 030104 developmental biology biological phenomena cell phenomena and immunity General Agricultural and Biological Sciences Astral microtubules Microtubule-Associated Proteins 030217 neurology & neurosurgery Cell Division HeLa Cells |
| Zdroj: | Current biology 31 (2021): 658–667.e5. doi:10.1016/j.cub.2020.10.096 info:cnr-pdr/source/autori:Polverino F.; Naso F.D.; Asteriti I.A.; Palmerini V.; Singh D.; Valente D.; Bird A.W.; Rosa A.; Mapelli M.; Guarguaglini G./titolo:The Aurora-A%2FTPX2 Axis Directs Spindle Orientation in Adherent Human Cells by Regulating NuMA and Microtubule Stability/doi:10.1016%2Fj.cub.2020.10.096/rivista:Current biology/anno:2021/pagina_da:658/pagina_a:667.e5/intervallo_pagine:658–667.e5/volume:31 |
| ISSN: | 1879-0445 |
| Popis: | Mitotic spindle orientation is a crucial process that defines the axis of cell division, contributing to daughter cell positioning and fate, and hence to tissue morphogenesis and homeostasis.1,2 The trimeric NuMA/LGN/Gαi complex, the major determinant of spindle orientation, exerts pulling forces on the spindle poles by anchoring astral microtubules (MTs) and dynein motors to the cell cortex.3,4 Mitotic kinases contribute to correct spindle orientation by regulating nuclear mitotic apparatus protein (NuMA) localization,5-7 among which the Aurora-A centrosomal kinase regulates NuMA targeting to the cell cortex in metaphase.8,9 Aurora-A and its activator targeting protein for Xklp2 (TPX2) are frequently overexpressed in cancer,10-12 raising the question as to whether spindle orientation is among the processes downstream the Aurora-A/TPX2 signaling axis altered under pathological conditions. Here, we investigated the role of TPX2 in the Aurora-A- and NuMA-dependent spindle orientation. We show that, in cultured adherent human cells, the interaction with TPX2 is required for Aurora-A to exert this function. We also show that Aurora-A, TPX2, and NuMA are part of a complex at spindle MTs, where TPX2 acts as a platform for Aurora-A regulation of NuMA. Interestingly, excess TPX2 does not influence NuMA localization but induces a "super-alignment" of the spindle axis with respect to the substrate, although an excess of Aurora-A induces spindle misorientation. These opposite effects are both linked to altered MT stability. Overall, our results highlight the importance of TPX2 for spindle orientation and suggest that spindle orientation is differentially sensitive to unbalanced levels of Aurora-A, TPX2, or the Aurora-A/TPX2 complex. |
| Databáze: | OpenAIRE |
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