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Plk1 regulates spindle orientation by phosphorylating NuMA in human cells

Shrividya Sana1, Riya Keshri1, Ashwathi Rajeevan1

  • 1Department of Microbiology and Cell Biology, Indian Institute of Science (IISc), Bangalore, India.

Life Science Alliance
|November 21, 2018
PubMed

Insights

Polo-like kinase 1 (Plk1) regulates cell division by controlling the positioning of the mitotic spindle. Plk1 directly phosphorylates NuMA, impacting its cortical localization for precise spindle orientation during metaphase.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Proper mitotic spindle orientation is crucial for accurate cell division and development in metazoans.
  • The NuMA/LGN/Gαi complex regulates spindle orientation by modulating cortical dynein levels during metaphase.

Purpose of the Study:

  • To elucidate the molecular mechanisms governing the spatiotemporal dynamics of the NuMA/LGN/Gαi complex during mitosis.
  • To investigate the role of Polo-like kinase 1 (Plk1) in regulating spindle orientation.

Main Methods:

  • Acute inactivation of Plk1 during metaphase.
  • Analysis of cortical dynein, NuMA, and LGN levels.
  • Investigation of NuMA's dynamic behavior at the cell cortex.
  • Co-immunoprecipitation and in vitro phosphorylation assays to study Plk1-NuMA interaction.

Main Results:

  • Plk1 inactivation enriches cortical dynein/NuMA/LGN levels, influencing spindle orientation via NuMA.
  • Plk1 inhibition alters NuMA's dynamic behavior at the cell cortex.
  • Plk1 directly interacts with and phosphorylates NuMA, affecting its cortical localization.
  • NuMA phosphorylation by Plk1 is essential for precise spindle orientation in metaphase.

Conclusions:

  • Plk1 acts through NuMA to regulate cortical dynein levels and spindle orientation.
  • Plk1-mediated phosphorylation of NuMA is a key mechanism for precise spindle orientation.
  • This study connects the spindle-pole pool of Plk1 to cortical NuMA, explaining how Plk1 gradients ensure error-free mitosis.

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