Erbin regulates NRG1 signaling and myelination

Yanmei Tao, Penggao Dai, Yu Liu, Sylvie Marchetto, Wen Cheng Xiong, Jean Paul Borg, Lin Mei

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Neuregulin 1 (NRG1) plays a critical role in myelination. However, little is known about regulatory mechanisms of NRG1 signaling. We show here that Erbin, a protein that contains leucine-rich repeats (LRR) and a PSD95-Dlg-Zol (PDZ) domain and that interacts specifically with ErbB2, is necessary for NRG1 signaling and myelination of peripheral nervous system (PNS). In Erbin null mice, myelinated axons were hypomyelinated with reduced expression of P0, a marker of mature myelinating Schwann cells (SCs), whereas unmyelinated axons were aberrantly ensheathed in Remak bundles, with increased numbers of axons in the bundles and in pockets. The morphological deficits were associated with decreased nerve conduction velocity and increased sensory threshold to mechanistic stimulation. These phenotypes were duplicated in erbin ΔC/ΔC mice, in which Erbin lost the PDZ domain to interact with ErbB2. Moreover, ErbB2 was reduced at protein levels in both Erbin mutant sciatic nerves, and ErbB2 became unstable and NRG1 signaling compromised when Erbin expression was suppressed. These observations indicate a critical role of Erbin in myelination and identify a regulatory mechanism of NRG1 signaling. Our results suggest that Erbin, via the PDZ domain, binds to and stabilizes ErbB2, which is necessary for NRG1 signaling that has been implicated in tumorigenesis, heart development, and neural function.

Original languageEnglish (US)
Pages (from-to)9477-9482
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number23
DOIs
StatePublished - Jun 9 2009

Keywords

  • Akt
  • ErbB2
  • PDZ
  • Protein stability
  • Schwann cells

ASJC Scopus subject areas

  • General

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    Tao, Y., Dai, P., Liu, Y., Marchetto, S., Xiong, W. C., Borg, J. P., & Mei, L. (2009). Erbin regulates NRG1 signaling and myelination. Proceedings of the National Academy of Sciences of the United States of America, 106(23), 9477-9482. https://doi.org/10.1073/pnas.0901844106