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Citation
Metcalfe, C., Mendoza-Topaz, C., Mieszczanek, J., Bienz, M. (2010). Stability elements in the LRP6 cytoplasmic tail confer efficient signalling upon DIX-dependent polymerization.  J. Cell Sci. 123(9): 1588--1599.
FlyBase ID
FBrf0210630
Publication Type
Research paper
Abstract

Wnt/beta-catenin signalling controls cell fates in development, tissue homeostasis and cancer. Wnt binding to Frizzled receptors triggers recruitment of Dishevelled to the plasma membrane and formation of a signalosome containing the LRP5/6 co-receptor, whose cytoplasmic tail (ctail) thus becomes phosphorylated at multiple PPP(S/T)Px(S/T) motifs. These then directly inhibit GSK3beta, which results in beta-catenin accumulation and signalling. Here, we revisit previous epistasis experiments, and show that Dishevelled signals through LRP5/6 in human cells and Drosophila embryos. To recapitulate this signalling event, and to define its functional elements, we fused the Dishevelled DIX domain to the LRP6 ctail, which forms cytoplasmic signalosomes with potent signalling activity mediated by its PPP(S/T)Px(S/T) motifs. Their phosphorylation and activity depends critically on DIX-mediated polymerization, and on multiple stability elements in the LRP6 ctail, including the T1479 epitope upstream of the membrane-proximal PPP(S/T)Px(S/T) motif. Thus, stable polymerization emerges as a key principle underlying the function of Dishevelled-dependent signalosomes.

PubMed ID
PubMed Central ID
PMC2858023 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Cell Sci.
    Title
    Journal of Cell Science
    Publication Year
    1966-
    ISBN/ISSN
    0021-9533
    Data From Reference
    Aberrations (1)
    Alleles (13)
    Genes (9)
    Natural transposons (1)
    Experimental Tools (1)
    Transgenic Constructs (8)