A nuclear variant of ErbB3 receptor tyrosine kinase regulates ezrin distribution and Schwann cell myelination.
A nuclear variant of ErbB3 receptor tyrosine kinase regulates ezrin distribution and Schwann cell myelination.
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DOI：
10.1523/jneurosci.5635-10.2011
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发表时间：
2011-03-30
期刊：
影响因子：
--
通讯作者：
Tapinos N
中科院分区：
文献类型：
--
作者：
Adilakshmi T;Ness-Myers J;Madrid-Aliste C;Fiser A;Tapinos N
Reciprocal interactions between glia and neurons are essential for the proper organization and function of the nervous system. Recently, the interaction between ErbB receptors (ErbB2 and ErbB3) on the surface of Schwann cells and neuronal Neuregulin-1 (NRG1) has emerged as the pivotal signal that controls Schwann cell development, association with axons, and myelination. To understand the function of NRG1-ErbB2/3 signaling axis in adult Schwann cell biology we are studying the specific role of ErbB3 receptor tyrosine kinase (RTK) since it is the receptor for NRG1 on the surface of Schwann cells. Here we show that alternative transcription initiation results in the formation of a nuclear variant of ErbB3 (nuc-ErbB3) in rat primary Schwann cells. Nuc-ErbB3 possesses a functional nuclear localization signal sequence and binds to chromatin. Using ChIP-ChIP arrays we identified the promoters that associate with nuc-ErbB3 and clustered the active promoters in Schwann cell gene expression. Nuc-ErbB3 regulates the transcriptional activity of ezrin and HMGB1 promoters while inhibition of nuc-ErbB3 expression results in reduced myelination and altered distribution of ezrin in the nodes of Ranvier. Finally, we reveal that NRG1 regulates the translation of nuc-ErbB3 in rat Schwann cells. For the first time, to our knowledge, we show that alternative transcription initiation from a gene that encodes a RTK is capable to generate a protein variant of the receptor with a distinct role in molecular and cellular regulation. We propose a new concept for the molecular regulation of myelination through the expression and distinct role of nuc-ErbB3.
