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Plk1 regulates spindle orientation by phosphorylating NuMA in human cells

Sana, S and Keshri, R and Rajeevan, A and Kapoor, S and Kotak, S (2018) Plk1 regulates spindle orientation by phosphorylating NuMA in human cells. In: Life Science Alliance, 1 (6).

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Official URL: https://doi.org/10.26508/lsa.201800223


Proper orientation of the mitotic spindle defines the correct division plane and is essential for accurate cell division and development. In metazoans, an evolutionarily conserved complex comprising of NuMA/LGN/Gαi regulates proper orientation of the mitotic spindle by orchestrating cortical dynein levels during metaphase. However, the molecular mechanisms that modulate the spatiotemporal dynamics of this complex during mitosis remain elusive. Here, we report that acute inactivation of Polo-like kinase 1 (Plk1) during metaphase enriches cortical levels of dynein/NuMA/LGN and thus influences spindle orientation. We establish that this impact of Plk1 on cortical levels of dynein/ NuMA/LGN is through NuMA, but not via dynein/LGN. Moreover, we reveal that Plk1 inhibition alters the dynamic behavior of NuMA at the cell cortex. We further show that Plk1 directly interacts and phosphorylates NuMA. Notably, NuMA-phosphorylation by Plk1 impacts its cortical localization, and this is needed for precise spindle orientation during metaphase. Overall, our finding connects spindle-pole pool of Plk1 with cortical NuMA and answers a long-standing puzzle about how spindle-pole Plk1 gradient dictates proper spindle orientation for error-free mitosis.

Item Type: Journal Article
Publication: Life Science Alliance
Publisher: Rockefeller University Press
Additional Information: The copyright for this article belongs to the Authors.
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 02 Sep 2022 04:11
Last Modified: 02 Sep 2022 04:11
URI: https://eprints.iisc.ac.in/id/eprint/76357

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