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Publication : Grb2-associated binder-1 is required for neuregulin-1-induced peripheral nerve myelination.

First Author  Shin YK Year  2014
Journal  J Neurosci Volume  34
Issue  22 Pages  7657-62
PubMed ID  24872569 Mgi Jnum  J:211333
Mgi Id  MGI:5574519 Doi  10.1523/JNEUROSCI.4947-13.2014
Citation  Shin YK, et al. (2014) Grb2-associated binder-1 is required for neuregulin-1-induced peripheral nerve myelination. J Neurosci 34(22):7657-62
abstractText  Grb2-associated binders (Gabs) are scaffolding proteins implicated in cell signaling via receptor tyrosine kinases including neuregulin-1(NRG1)-ErbB receptor signaling, which is essential for peripheral nerve myelination. Here, we show that the conditional removal of Gab1 from Schwann cells resulted in hypomyelination and abnormal development of Remak bundles. In contrast, hypomyelination was not observed in conventional Gab2 knock-out mice. Tyrosine phosphorylation of Gab1, but not Gab2, in sciatic nerves was upregulated during the myelination period and was found to be suppressed in NRG1-type III(+/-) mice, which display a hypomyelinated phenotype similar to that observed in Gab1 knock-out mice. Gab1 knock-out and NRG1-type III(+/-) mice both exhibited reduced extracellular signal-regulated kinase activity in myelinating nerves. In addition, Krox20, a transcription factor that is critical for myelination, has been identified as a target of the NRG1-Gab1 pathway during the myelination process. Our findings suggest that Gab1 is an essential component of NRG1-type III signaling during peripheral nerve development.
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