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Your search keyword '"Alfieri, Andrea"' showing total 2 results
Start Over Author "Alfieri, Andrea" Publisher nature pub. group
2 results on '"Alfieri, Andrea"'

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

Author

Pirovano L, Culurgioni S, Carminati M, Alfieri A, Monzani S, Cecatiello V, Gaddoni C, Rizzelli F, Foadi J, Pasqualato S, and Mapelli M

Subjects
Antigens, Nuclear chemistry, Antigens, Nuclear genetics, Antigens, Nuclear isolation & purification, Caco-2 Cells, Cell Cycle Proteins, Crystallography, X-Ray, Dynactin Complex metabolism, Dyneins metabolism, Gene Knockdown Techniques, HEK293 Cells, HeLa Cells, Humans, Intracellular Signaling Peptides and Proteins chemistry, Intracellular Signaling Peptides and Proteins genetics, Intracellular Signaling Peptides and Proteins isolation & purification, Microtubules metabolism, Nuclear Matrix-Associated Proteins chemistry, Nuclear Matrix-Associated Proteins genetics, Nuclear Matrix-Associated Proteins isolation & purification, Protein Binding physiology, Protein Multimerization physiology, RNA, Small Interfering metabolism, Recombinant Proteins chemistry, Recombinant Proteins genetics, Recombinant Proteins isolation & purification, Recombinant Proteins metabolism, Antigens, Nuclear metabolism, Cell Polarity, Intracellular Signaling Peptides and Proteins metabolism, Nuclear Matrix-Associated Proteins metabolism, Spindle Apparatus metabolism
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.

Published
2019
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2. Concomitant binding of Afadin to LGN and F-actin directs planar spindle orientation.

Author

Carminati M, Gallini S, Pirovano L, Alfieri A, Bisi S, and Mapelli M

Subjects
Actins analysis, Amino Acid Sequence, Caco-2 Cells, Crystallography, X-Ray, HeLa Cells, Humans, Intracellular Signaling Peptides and Proteins analysis, Microfilament Proteins analysis, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Interaction Maps, Spindle Apparatus chemistry, Spindle Apparatus metabolism, Actins metabolism, Intracellular Signaling Peptides and Proteins metabolism, Microfilament Proteins metabolism, Spindle Apparatus ultrastructure
Abstract

Polarized epithelia form by oriented cell divisions in which the mitotic spindle aligns parallel to the epithelial plane. To orient the mitotic spindle, cortical cues trigger the recruitment of NuMA-dynein-based motors, which pull on astral microtubules via the protein LGN. We demonstrate that the junctional protein Afadin is required for spindle orientation and correct epithelial morphogenesis of Caco-2 cysts. Molecularly, Afadin binds directly and concomitantly to F-actin and to LGN. We determined the crystallographic structure of human Afadin in complex with LGN and show that it resembles the LGN-NuMA complex. In mitosis, Afadin is necessary for cortical accumulation of LGN and NuMA above the spindle poles, in an F-actin-dependent manner. Collectively, our results depict Afadin as a molecular hub governing the enrichment of LGN and NuMA at the cortex. To our knowledge, Afadin is the first-described mechanical anchor between dynein and cortical F-actin.

Published
2016
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