Bex3 Dimerization Regulates NGF-Dependent Neuronal Survival and Differentiation by Enhancing trkA Gene Transcription. Academic Article uri icon

Overview

abstract

  • The development of the nervous system is a temporally and spatially coordinated process that relies on the proper regulation of the genes involved. Neurotrophins and their receptors are directly responsible for the survival and differentiation of sensory and sympathetic neurons; however, it is not fully understood how genes encoding Trk neurotrophin receptors are regulated. Here, we show that rat Bex3 protein specifically regulates TrkA expression by acting at the trkA gene promoter level. Bex3 dimerization and shuttling to the nucleus regulate the transcription of the trkA promoter under basal conditions and also enhance nerve growth factor (NGF)-mediated trkA promoter activation. Moreover, qChIP assays indicate that Bex3 associates with the trkA promoter within a 150 bp sequence, immediately upstream from the transcription start site, which is sufficient to mediate the effects of Bex3. Consequently, the downregulation of Bex3 using shRNA increases neuronal apoptosis in NGF-dependent sensory neurons deprived of NGF and compromises PC12 cell differentiation in response to NGF. Our results support an important role for Bex3 in the regulation of TrkA expression and in NGF-mediated functions through modulation of the trkA promoter.

publication date

  • May 6, 2015

Research

keywords

  • Apoptosis Regulatory Proteins
  • Cell Differentiation
  • Nerve Growth Factor
  • Protein Multimerization
  • Receptor, trkA
  • Transcription, Genetic

Identity

PubMed Central ID

  • PMC6605261

Scopus Document Identifier

  • 84929379976

Digital Object Identifier (DOI)

  • 10.1111/j.1600-0854.2010.01156.x

PubMed ID

  • 25948268

Additional Document Info

volume

  • 35

issue

  • 18