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

Laura Pirovano, Simone Culurgioni, Manuel Carminati, Andrea Alfieri, Silvia Monzani, Valentina Cecatiello, Chiara Gaddoni, Francesca Rizzelli, James Foadi, Sebastiano Pasqualato and Marina Mapelli ()
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Laura Pirovano: IEO, European Institute of Oncology IRCCS
Simone Culurgioni: IEO, European Institute of Oncology IRCCS
Manuel Carminati: IEO, European Institute of Oncology IRCCS
Andrea Alfieri: IEO, European Institute of Oncology IRCCS
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

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-09999-w

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