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Curr Biol. 2015 Jan 5;25(1):61-8. doi: 10.1016/j.cub.2014.10.052. Epub 2014 Dec 4.

Aurora kinases phosphorylate Lgl to induce mitotic spindle orientation in Drosophila epithelia.

Author information

1
Epithelial Biology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields, London WC2A 3LY, UK.
2
Epithelial Biology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields, London WC2A 3LY, UK. Electronic address: barry.thompson@cancer.org.uk.

Abstract

The Lethal giant larvae (Lgl) protein was discovered in Drosophila as a tumor suppressor in both neural stem cells (neuroblasts) and epithelia. In neuroblasts, Lgl relocalizes to the cytoplasm at mitosis, an event attributed to phosphorylation by mitotically activated aPKC kinase and thought to promote asymmetric cell division. Here we show that Lgl also relocalizes to the cytoplasm at mitosis in epithelial cells, which divide symmetrically. The Aurora A and B kinases directly phosphorylate Lgl to promote its mitotic relocalization, whereas aPKC kinase activity is required only for polarization of Lgl. A form of Lgl that is a substrate for aPKC, but not Aurora kinases, can restore cell polarity in lgl mutants but reveals defects in mitotic spindle orientation in epithelia. We propose that removal of Lgl from the plasma membrane at mitosis allows Pins/LGN to bind Dlg and thus orient the spindle in the plane of the epithelium. Our findings suggest a revised model for Lgl regulation and function in both symmetric and asymmetric cell divisions.

PMID:
25484300
PMCID:
PMC4291145
DOI:
10.1016/j.cub.2014.10.052
[Indexed for MEDLINE]
Free PMC Article

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