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Hexameric NuMA:LGN structures promote multivalent interactions required for planar epithelial divisions

Author

Listed:
  • Laura Pirovano

    (IEO, European Institute of Oncology IRCCS)

  • Simone Culurgioni

    (IEO, European Institute of Oncology IRCCS
    Exscientia Ltd.)

  • Manuel Carminati

    (IEO, European Institute of Oncology IRCCS
    MRC Laboratory of Molecular Biology)

  • Andrea Alfieri

    (IEO, European Institute of Oncology IRCCS
    Università degli Studi di Milano)

  • Silvia Monzani

    (IEO, European Institute of Oncology IRCCS)

  • Valentina Cecatiello

    (IEO, European Institute of Oncology IRCCS)

  • Chiara Gaddoni

    (IEO, European Institute of Oncology IRCCS)

  • Francesca Rizzelli

    (IEO, European Institute of Oncology IRCCS)

  • James Foadi

    (University of Bath)

  • Sebastiano Pasqualato

    (IEO, European Institute of Oncology IRCCS)

  • Marina Mapelli

    (IEO, European Institute of Oncology IRCCS)

Abstract

Cortical force generators connect epithelial polarity sites with astral microtubules, allowing dynein movement to orient the mitotic spindle as astral microtubules depolymerize. Complexes of the LGN and NuMA proteins, fundamental components of force generators, are recruited to the cortex by Gαi-subunits of heterotrimeric G-proteins. They associate with dynein/dynactin and activate the motor activity pulling on astral microtubules. The architecture of cortical force generators is unknown. Here we report the crystal structure of NuMA:LGN hetero-hexamers, and unveil their role in promoting the assembly of active cortical dynein/dynactin motors that are required in orchestrating oriented divisions in polarized cells. Our work elucidates the basis for the structural organization of essential spindle orientation motors.

Suggested Citation

  • Laura Pirovano & Simone Culurgioni & Manuel Carminati & Andrea Alfieri & Silvia Monzani & Valentina Cecatiello & Chiara Gaddoni & Francesca Rizzelli & James Foadi & Sebastiano Pasqualato & Marina Mape, 2019. "Hexameric NuMA:LGN structures promote multivalent interactions required for planar epithelial divisions," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09999-w
    DOI: 10.1038/s41467-019-09999-w
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    Cited by:

    1. Maria Fankhaenel & Farahnaz S. Golestan Hashemi & Larissa Mourao & Emily Lucas & Manal M. Hosawi & Paul Skipp & Xavier Morin & Colinda L.G.J. Scheele & Salah Elias, 2023. "Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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