RT Journal Article
SR Electronic
T1 Grb2-Associated Binder-1 Is Required for Neuregulin-1-Induced Peripheral Nerve Myelination
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7657
OP 7662
DO 10.1523/JNEUROSCI.4947-13.2014
VO 34
IS 22
A1 Yoon Kyung Shin
A1 So Young Jang
A1 So Young Park
A1 Joo Youn Park
A1 Jong Kuk Kim
A1 Jong Phil Kim
A1 Duk Joon Suh
A1 Hye Jeong Lee
A1 Hwan Tae Park
YR 2014
UL http://www.jneurosci.org/content/34/22/7657.abstract
AB 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.