Fig. 6.

Model of the role of Insc:LGN complex in asymmetric divisions. a Schematic diagram depicting the organization of cortical domains and mitotic spindle motors in murine mitotic mammary stem cells. b Schematic representation of the asymmetric function of Insc:LGN tetramers supported by our study. Initally, Insc:LGN complexes are recruited at the apical membrane by direct binding of LGN to Gαi-GDP molecules, and by association of Insc with Par3. Cooperative binding to LGN-GoLoco motifs favors Gαi-GDP apical clustering. Later, a Gαi GTP-cycle, likely catalyzed by a GEF such as Ric-8A, dissociates Gαi from Insc:LGN, generating a localized pool of Gαi-GTP molecules, which upon GTP hydrolysis recruits LGN:NuMA:Dynein complexes at the apical site. According to this model, stable Insc:LGN assemblies couple asymmetric fate specification with apico-basal spindle orientation by Gαi-GDP transfer