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Citation
Weber, U., Mlodzik, M. (2017). APC/C(Fzr/Cdh1)-Dependent Regulation of Planar Cell Polarity Establishment via Nek2 Kinase Acting on Dishevelled.  Dev. Cell 40(1): 53--66.
FlyBase ID
FBrf0234479
Publication Type
Research paper
Abstract

The Anaphase-Promoting Complex/Cyclosome (APC/C) is an E3 ubiquitin ligase, well known for its role in cell-cycle progression. However, it has been linked to additional functions, mainly in neuronal contexts, when using the co-activator Cdh1/Fzr. Here, our data indicate a post-mitotic requirement for the APC/C(Fzr/Cdh1) in epithelial cell patterning and planar cell polarity (PCP) in Drosophila. PCP signaling is critical for development by establishing cellular asymmetries and orientation within the plane of an epithelium, via differential localization of distinct complexes of core PCP factors. Loss of APC/C function leads to reduced levels of Dishevelled (Dsh), a core PCP factor. The effect of APC/C on Dsh is mediated by Nek2 kinase, which can phosphorylate Dsh and is a direct APC/C(Fzr/Cdh1) substrate. We have thus uncovered a pathway of regulation whereby APC/C(Fzr/Cdh1) negatively regulates Nek2, which negatively regulates Dsh, to ensure its proper stoichiometric requirement and localization during PCP establishment.

Graphical Abstract
Obtained with permission from Cell Press.
PubMed ID
PubMed Central ID
PMC5225046 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Dev. Cell
    Title
    Developmental Cell
    Publication Year
    2001-
    ISBN/ISSN
    1534-5807 1878-1551
    Data From Reference
    Alleles (46)
    Genes (17)
    Natural transposons (1)
    Insertions (3)
    Experimental Tools (4)
    Transgenic Constructs (35)