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    Dev Biol. 2007 Oct 15;310(2):250-63. Epub 2007 Aug 2.

    Wise retained in the endoplasmic reticulum inhibits Wnt signaling by reducing cell surface LRP6.

    Guidato S, Itasaki N.

    Source

    Division of Developmental Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK.

    Abstract

    The Wnt signaling pathway is tightly regulated by extracellular and intracellular modulators. Wise was isolated as a secreted protein capable of interacting with the Wnt co-receptor LRP6. Studies in Xenopus embryos revealed that Wise either enhances or inhibits the Wnt pathway depending on the cellular context. Here we show that the cellular localization of Wise has distinct effects on the Wnt pathway readout. While secreted Wise either synergizes or inhibits the Wnt signals depending on the partner ligand, ER-retained Wise consistently blocks the Wnt pathway. ER-retained Wise reduces LRP6 on the cell surface, making cells less susceptible to the Wnt signal. This study provides a cellular mechanism for the action of Wise and introduces the modulation of cellular susceptibility to Wnt signals as a novel mechanism of the regulation of the Wnt pathway.

    PMID:
    17765217
    [PubMed - indexed for MEDLINE]

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