Journal of Molecular Neuroscience

, Volume 38, Issue 2, pp 152–158

NRIF is a Regulator of Neuronal Cholesterol Biosynthesis Genes

  • Zeljka Korade
  • Rajappa S. Kenchappa
  • Karoly Mirnics
  • Bruce D. Carter
Article

DOI: 10.1007/s12031-008-9136-9

Cite this article as:
Korade, Z., Kenchappa, R.S., Mirnics, K. et al. J Mol Neurosci (2009) 38: 152. doi:10.1007/s12031-008-9136-9

Abstract

Cholesterol is a critical component of neuronal membranes, required for normal signal transduction. We showed previously that adult hippocampal neurons co-express high levels of cholesterogenic enzymes, and that their expression is under the control of the p75 neurotrophin receptor (p75NTR). Most of the cellular effects of p75NTR are mediated via interacting proteins, including neurotrophin receptor interacting factor (NRIF). In this study, we tested the hypothesis that p75NTR-dependent regulation of cholesterol and lipid biosynthesis genes is mediated by NRIF. We found that in vitro down regulation of NRIF expression decreased the mRNA for two main cholesterogenic enzymes, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr; EC 2.3.3.10) and 7-dehydrocholesterol reductase (Dhcr7; EC 1.3.1.21). Further analyses revealed that NRIF-dependent and Dhcr7-dependent transcriptional changes show a high degree of overlap, and that NRIF reduction resulted in reduced expression of sterol-sensing domain protein SCAP, followed by a decrease in mRNA levels of SRE-motif containing genes (HMGCR, FASN, SREBP2, S1P, and SQS1). Finally, a reduction in cholesterol biosynthesis-related gene expression was also observed in hippocampal tissue of mice with NRIF deletion. Our combined in vitro and in vivo studies suggest that hippocampal neuronal cholesterol biosynthesis is regulated through the p75NTR interacting factor NRIF.

Keywords

Cholesterol Neuroblastoma NRIF KO mice SREBP Gene expression p75NTR Neurotrophin 

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  • Zeljka Korade
    • 1
    • 2
  • Rajappa S. Kenchappa
    • 1
  • Karoly Mirnics
    • 2
    • 3
  • Bruce D. Carter
    • 1
    • 2
  1. 1.Department of BiochemistryVanderbilt University School of MedicineNashvilleUSA
  2. 2.Vanderbilt Kennedy Center for Research on Human DevelopmentNashvilleUSA
  3. 3.Department of PsychiatryVanderbilt UniversityNashvilleUSA

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