Abstract
Neuregulin-1 (Nrg1) provides a key axonal signal that regulates Schwann cell proliferation, migration and myelination through binding to ErbB2/3 receptors. The analysis of a number of genetic models has unmasked fundamental mechanisms underlying the specificity of the Nrg1/ErbB signaling axis. Differential expression of Nrg1 isoforms, Nrg1 processing, and ErbB receptor localization and trafficking represent important regulatory themes in the control of Nrg1/ErbB function. Nrg1 binding to ErbB2/3 receptors results in the activation of intracellular signal transduction pathways that initiate changes in Schwann cell behavior. Here, we review data that has defined the role of key Nrg1/ErbB signaling components like Shp2, ERK1/2, FAK, Rac1/Cdc42 and calcineurin in development of the Schwann cell lineage in vivo. Many of these regulators receive converging signals from other cues that are provided by Notch, integrin or G-protein coupled receptors. Signaling by multiple extracellular factors may act as key modifiers and allow Schwann cells at different developmental stages to respond in distinct manners to the Nrg1/ErbB signal.
Original language | English (US) |
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Pages (from-to) | 922-928 |
Number of pages | 7 |
Journal | Seminars in Cell and Developmental Biology |
Volume | 21 |
Issue number | 9 |
DOIs | |
State | Published - Dec 2010 |
Externally published | Yes |
Keywords
- Erbin
- Erk
- Myelination
- Neuregulin
- Shp2
ASJC Scopus subject areas
- Developmental Biology
- Cell Biology