title: E-cadherin enhances neuregulin signaling and promotes Schwann cell myelination.
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.
authors.affiliation: Department of Biological Sciences, Rutgers University, Newark, New Jersey.
authors.forename: Sayantani
authors.initials: S
authors.lastname: Basak
authors.affiliation: Department of Biological Sciences, Rutgers University, Newark, New Jersey.
authors.forename: Darshan J
authors.initials: DJ
authors.lastname: Desai
authors.affiliation: Department of Biological Sciences, Rutgers University, Newark, New Jersey.
authors.forename: Esther H
authors.initials: EH
authors.lastname: Rho
authors.affiliation: Department of Biological Sciences, Rutgers University, Newark, New Jersey.
authors.forename: Roselle
authors.initials: R
authors.lastname: Ramos
authors.affiliation: Department of Biological Sciences, Rutgers University, Newark, New Jersey.
authors.forename: Patrice
authors.initials: P
authors.lastname: Maurel
authors.affiliation: Department of Biological Sciences, Rutgers University, Newark, New Jersey.
authors.forename: Haesun A
authors.initials: HA
authors.lastname: Kim
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D018920:Coculture Techniques; D066246:ErbB Receptors / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000254:growth & development / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000502:physiology*; D020890:Neuregulin-1 / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D012583:Schwann Cells / Q000502:physiology*; D012584:Sciatic Nerve / Q000254:growth & development / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D015820:Cadherins; D020890:Neuregulin-1; D066246:ErbB Receptors
keywords: DRG; Nrg1 type III; PI3-kinase; SCG; cell adhesion; erbB2; myelin