NRAGE is a negative regulator of nerve growth factor-stimulated neurite outgrowth in PC12 cells mediated through TrkA-ERK signaling
✍ Scribed by Zhenhua Feng; Kaizhen Li; Mei Liu; Chuanjun Wen
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 338 KB
- Volume
- 88
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
NRAGE, also denominated as MAGE‐D1 or Dlxin‐1, is firstly identified as a molecule interacting with NGF low affinity receptor p75NTR. It facilitates cell cycle arrest and NGF‐dependent neuronal apoptosis. Here we report that NRAGE is downregulated while p75NTR is upregulated during the process of NGF‐induced neuronal differentiation of PC12 cells. Knockdown of NRAGE by RNA interference accelerates NGF‐mediated neurite outgrowth. In addition, in the NRAGE‐suppressed cells, NGF‐induced ERK activation is increased and this activation is MEK‐dependent. Conversely, NRAGE overexpression significantly represses NGF‐induced ERK activation. Further studies revealed that NRAGE downregulates TrkA expression through a post‐transcriptional manner and thereby blocks NGF‐induced TrkA phosphrylation at tyrosine‐490. Altogether, these data indicate for the first time that NRAGE is an endogenous inhibitor for NGF‐induced neuronal differentiation of PC12 cells by regulating TrkA‐ERK signaling. © 2010 Wiley‐Liss, Inc.