Inscuteable and NuMA proteins bind competitively to Leu-Gly-Asn repeat-enriched protein (LGN) during asymmetric cell divisions

Simone Culurgioni, Andrea Alfieri, Valentina Pendolino, Federica Laddomada, Marina Mapelli

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Coupling of spindle orientation to cellular polarity is a prerequisite for epithelial asymmetric cell divisions. The current view posits that the adaptor Inscuteable (Insc) bridges between Par3 and the spindle tethering machinery assembled on NuMA:LGN:Gαi GDP, thus triggering apico-basal spindle orientation. The crystal structure of the Drosophila ortholog of LGN (known as Pins) in complex with Insc reveals a modular interface contributed by evolutionary conserved residues. The structure also identifies a positively charged patch of LGN binding to an invariant EPE-motif present on both Insc and NuMA. In vitro competition assays indicate that Insc competes with NuMA for LGN binding, displaying a higher affinity, and that it is capable of opening the LGN conformational switch. The finding that Insc and NuMA are mutually exclusive interactors of LGN challenges the established model of force generators assembly, which we revise on the basis of the newly discovered biochemical properties of the intervening components.

Original languageEnglish
Pages (from-to)20998-21003
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number52
DOIs
Publication statusPublished - Dec 27 2011

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Asymmetric Cell Division
Drosophila
Epithelial Cells
Proteins
In Vitro Techniques

ASJC Scopus subject areas

  • General

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Inscuteable and NuMA proteins bind competitively to Leu-Gly-Asn repeat-enriched protein (LGN) during asymmetric cell divisions. / Culurgioni, Simone; Alfieri, Andrea; Pendolino, Valentina; Laddomada, Federica; Mapelli, Marina.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 52, 27.12.2011, p. 20998-21003.

Research output: Contribution to journalArticle

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