Erbin regulates mitogen-activated protein (MAP) kinase activation and MAP kinase-dependent interactions between merlin and adherens junction protein complexes in Schwann cells

Reshma Rangwala, Fatima Banine, Jean Paul Borg, Larry S. Sherman

    Research output: Contribution to journalArticle

    60 Scopus citations

    Abstract

    Biallelic mutations in the neurofibromatosis 2 (NF2) gene are linked to schwannoma and meningioma tumorigenesis. Cells with NF2 mutations exhibit elevated levels of phosphorylated extracellular signal-regulated kinase (ERK) and aberrant cell-cell and cell-matrix contacts. The NF2 gene product, merlin, associates with adherens junction protein complexes, suggesting that part of its function as a tumor suppressor involves regulating cell junctions. Here, we find that a novel PDZ protein, called erbin, binds directly to the merlin-binding partner, EBP0, and regulates adherens junction dissociation through a MAP kinase-dependent mechanism. Reducing erbin expression using a targeted siRNA in primary cultures of Schwann cells results in altered cell-cell interactions, disruption of E-cadherin adherens junctions, increased cell proliferation, and elevated levels of phosphorylated ERK, all phenotypes observed in cells that lack merlin. Reduction of erbin expression also results in the dissociation of merlin from adherens junction proteins and an increase in the levels of phosphorylated merlin. These phenotypes can be rescued if cells with reduced levels of erbin are treated with a pharmacological inhibitor of ERK kinase. Collectively, these data indicate that erbin regulates MAP kinase activation in Schwann cells and suggest that erbin links merlin to both adherens junction protein complexes and the MAP kinase signaling pathway.

    Original languageEnglish (US)
    Pages (from-to)11790-11797
    Number of pages8
    JournalJournal of Biological Chemistry
    Volume280
    Issue number12
    DOIs
    StatePublished - Mar 25 2005

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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