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

DOI: 10.1038/s41467-019-09999-w DOI Help

Authors: Laura Pirovano (IEO, European Institute of Oncology) , Simone Culurgioni (IEO, European Institute of Oncology) , Manuel Carminati (IEO, European Institute of Oncology) , Andrea Alfieri (IEO, European Institute of Oncology) , Silvia Monzani (IEO, European Institute of Oncology) , Valentina Cecatiello (IEO, European Institute of Oncology) , Chiara Gaddoni (IEO, European Institute of Oncology) , Francesca Rizzelli (IEO, European Institute of Oncology) , James Foadi (Diamond Light Source) , Sebastiano Pasqualato (IEO, European Institute of Oncology) , Marina Mapelli (IEO, European Institute of Oncology)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 10

State: Published (Approved)
Published: May 2019
Diamond Proposal Number(s): 5966 , 5967

Open Access Open Access

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.

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography

Other Facilities: Swiss Light Source; European Synchrotron Radiation Facility