Inhibition of neuronal process outgrowth and neuronal specific gene activation by the Brn-3b transcription factor.

The Journal of Biological Chemistry
M D SmithD S Latchman

Abstract

The differentiation of the ND7 neuronal cell line to a nondividing phenotype bearing numerous neurite processes is accompanied by a dramatic increase in the levels of the activating POU family transcription factor Brn-3a and a corresponding fall in the levels of the closely related inhibitory factor Brn-3b. We have previously shown that the artificial overexpression of Brn-3a in these cells can induce neurite outgrowth and the activation of genes encoding synaptic vesicle proteins in the absence of a differentiation-inducing stimulus. Here we show that overexpression of Brn-3b can reduce process outgrowth and synaptic vesicle gene expression following exposure to a stimulus which would normally induce differentiation. These inhibitory effects are abolished by altering a single amino acid in the POU homeodomain of Brn-3b to its equivalent in Brn-3a. The converse mutation in Brn-3a allows it to inhibit process outgrowth in response to a differentiation-inducing stimulus. Hence a single amino acid difference results in these closely related factors having opposite effects and allows the balance between them to regulate differentiation.

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Citations

Jan 14, 1998·Brain Research. Molecular Brain Research·Z C DeansD S Latchman
Jan 21, 2000·Brain Research. Molecular Brain Research·M D SmithD S Latchman
Nov 15, 2002·Neuroscience Letters·Vishwanie Budhram-MahadeoDavid S Latchman
Apr 4, 2003·Neuroscience Letters·Alexandra ZourlidouDavid S Latchman
Jul 27, 2001·The International Journal of Biochemistry & Cell Biology·V Budhram-MahadeoD S Latchman
Feb 6, 2008·Molecular and Cellular Neurosciences·James K J DissDavid S Latchman
Oct 18, 2005·Brain Research. Molecular Brain Research·Richa SudSally J Dawson
Jan 31, 2006·Expert Opinion on Therapeutic Targets·Vishwanie S Budhram-Mahadeo, David S Latchman
Nov 14, 2007·American Journal of Human Genetics·Elizabeth SpiteriDaniel H Geschwind
Sep 21, 2005·Journal of Cellular Biochemistry·Pei WangChung-Liang Chien
Aug 22, 1997·The Journal of Biological Chemistry·M D SmithD S Latchman
Feb 19, 2004·The Journal of Biological Chemistry·Shazia IrshadVishwanie Budhram-Mahadeo
Apr 13, 1999·Journal of Cellular Physiology·D S Latchman
Mar 29, 2001·Molecular and Cellular Neurosciences·M D SmithD S Latchman

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