On the inscrutable role of Inscuteable: structural basis and functional implications for the competitive binding of NuMA and Inscuteable to LGN
نویسندگان
چکیده
Alignment of the mitotic spindle to the cellular polarity axis is a prerequisite for asymmetric cell divisions. The protein network coordinating the spindle position with cortical polarity includes the molecular machinery pulling on astral microtubules, which is assembled on conserved NuMA:LGN:Gαi complexes, the polarity proteins Par3:Par6:aPKC and an adaptor molecule known as Inscuteable (Insc). To date, all these components were assumed to enter a macromolecular complex localized at polarity sites in mitosis. However, recent structural studies revealed the Insc and NuMA are mutually exclusive interactors of LGN, implying that the molecular mechanism of spindle coupling to polarity is more sophisticated than has been believed to date.
منابع مشابه
Inscuteable and NuMA proteins bind competitively to Leu-Gly-Asn repeat-enriched protein (LGN) during asymmetric cell divisions.
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 NuMALGNGαi(GDP), thus triggering apico-basal spindle orientation. The crystal structure of the Drosophila ortholog of LGN (known as Pins) in complex with ...
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LGN is closely related to a Drosophila protein, Partner of inscuteable (Pins), which is required for polarity establishment and asymmetric cell divisions during embryonic development. In mammalian cells, LGN binds with high affinity to the C-terminal tail of NuMA, a large nuclear protein that is required for spindle organization, and accumulates at the spindle poles during mitosis. LGN also reg...
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During asymmetric cell division, alignment of the mitotic spindle with the cell polarity axis ensures that the cleavage furrow separates fate determinants into distinct daughter cells. The protein Inscuteable (Insc) is thought to link cell polarity and spindle positioning in diverse systems by binding the polarity protein Bazooka (Baz; aka Par-3) and the spindle orienting protein Partner of Ins...
متن کاملEvidence for dynein and astral microtubule–mediated cortical release and transport of Gαi/LGN/NuMA complex in mitotic cells
Spindle positioning is believed to be governed by the interaction between astral microtubules and the cell cortex and involve cortically anchored motor protein dynein. How dynein is recruited to and regulated at the cell cortex to generate forces on astral microtubules is not clear. Here we show that mammalian homologue of Drosophila Pins (Partner of Inscuteable) (LGN), a Gαi-binding protein th...
متن کاملA protein complex containing Inscuteable and the Gα-binding protein Pins orients asymmetric cell divisions in Drosophila
BACKGROUND In the fruit fly Drosophila, the Inscuteable protein localises to the apical cell cortex in neuroblasts and directs both the apical-basal orientation of the mitotic spindle and the basal localisation of the protein determinants Numb and Prospero during mitosis. Asymmetric localisation of Inscuteable is initiated during neuroblast delamination by direct binding to Bazooka, an apically...
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عنوان ژورنال:
دوره 2 شماره
صفحات -
تاریخ انتشار 2012