Poster abstracts

Poster number 76 submitted by Chhavy Tep

BDNF promotes myelination by activating ErbB2 in Schwann cells

Chhavy Tep (OSBP/OSU), Mi Lyang Kim (MCDB/OSU), Allison S. Limpert (Dept of Biochemistry and Molecular biology, USC), Jonah Chan (Dept of Biochemistry and Molecular Biology/USC), Bruce Carter (Dept of Biochemistry/Vanderbilt University), Sung Ok Yoon (MCB/OSU)

Abstract:
BDNF and neuregulin1 type III have been shown to promote myelination in the PNS, acting at Schwann cell surface through p75 and ErbB2/3, respectively. Here, we report that BDNF promotes myelination by inducing formation of a complex between p75 and ErbB2 via Par3 at the axoglial junction of the Schwann cell. This complex was found to activate Rac1, since Par3 knockdown disrupted the receptor complex, resulting in reduced BDNF-dependent Rac1 activation in Schwann cells. Of the two receptors, ErbB2 appears to be the principle signaling receptor that activates Rac1, while p75 acts as a ligand binding partner, as BDNF induced tyrosine phosphorylation of ErbB2, and inhibition of ErbB2 kinase activity led to complete blocking of BDNF-dependent Rac1 activation. In line with these data, RacGTP levels decreased in p75 knockout mice and knockdown of p75 in Schwann cells resulted in attenuation of myelination. This report thus identifies p75 and ErbB2 as a new coreceptor unit that responds to BDNF, and activates Rac1 in a spatially restricted manner

Keywords: myelination, Schwann cell, p75