E-Cadherin enhances neuregulin signaling and promotes Schwann cell myelination

Sayantani Basak, Darshan J. Desai, Esther H. Rho, Roselle Ramos, Patrice Maurel, Haesun A. Kim

    Research output: Contribution to journalArticlepeer-review

    15 Scopus citations

    Abstract

    In myelinating Schwann cells, E-cadherin is a component of the adherens junctions that stabilize the architecture of the noncompact myelin region. In other cell types, E-cadherin has been considered as a signaling receptor that modulates intracellular signal transduction and cellular responses. To determine whether E-cadherin plays a regulatory role during Schwann cell myelination, we investigated the effects of E-cadherin deletion and over-expression in Schwann cells. In vivo, Schwann cell-specific E-cadherin ablation results in an early myelination delay. In Schwann cell-dorsal root ganglia neuron co-cultures, E-cadherin deletion attenuates myelin formation and shortens the myelin segment length. When over-expressed in Schwann cells, E-cadherin improves myelination on Nrg1 type III+/- neurons and induces myelination on normally non-myelinated axons of sympathetic neurons. The pro-myelinating effect of E-cadherin is associated with an enhanced Nrg1-erbB receptor signaling, including activation of the downstream Akt and Rac. Accordingly, in the absence of E-cadherin, Nrg1-signaling is diminished in Schwann cells. Our data also show that E-cadherin expression in Schwann cell is induced by axonal Nrg1 type III, indicating a reciprocal interaction between E-cadherin and the Nrg1 signaling. Altogether, our data suggest a regulatory function of E-cadherin that modulates Nrg1 signaling and promotes Schwann cell myelin formation.

    Original languageEnglish (US)
    Pages (from-to)1522-1536
    Number of pages15
    JournalGLIA
    Volume63
    Issue number9
    DOIs
    StatePublished - Sep 2015

    All Science Journal Classification (ASJC) codes

    • Neurology
    • Cellular and Molecular Neuroscience

    Keywords

    • Cell adhesion
    • DRG
    • Myelin
    • Nrg1 type III
    • PI3-kinase
    • SCG
    • erbB2

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