Regulation of Neurite Outgrowth and SNAP-25 Gene Expression by the Brn-3a Transcription Factor (*)
- Nic D. Lakin(1),
- Peter J. Morris(1),
- Thomas Theil(2),
- Tom N. Sato(3)(§),
- Tarik Möröy(2),
- Michael C. Wilson(3) and
- David S. Latchman(1)(¶)
- From the (1) Medical Molecular Biology Unit, Department of Molecular Pathology, University College London Medical School, The Windeyer Building, Cleveland Street, London, W1P 6DB, United Kingdom,
- (2)Institut für Molekularbiologie und Tumorforschung, Philipps Universität Marburg, Emil Mankopff-Strasse 2, D-35037, Marburg, Federal Republic of Germany, and the
- (3)Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037
- ¶ To whom correspondence should be addressed.
Abstract
SNAP-25 is a presynaptic nerve terminal protein which is also essential for the process of neurite outgrowth in vivo and in vitro. However the processes regulating its expression have not been characterized previously. We show that the gene encoding this protein, SNAP, is strongly activated by the Brn-3a POU (Pit-Oct-Unc) family transcription factor. Expression of both Brn-3a and SNAP-25 increases when ND7 neuronal cells are induced to extend neurite processes by serum removal. Inhibition of Brn-3a expression in these cells inhibits SNAP-25 expression and abolishes the neurite outgrowth that normally occurs in response to serum removal. These results identify Brn-3a as the first transcription factor having a role in process outgrowth in neuronal cells acting, at least in part, via the activation of SNAP-25 gene expression.
Footnotes
-
↵* This work was supported by Action Research and the Medical Research Council (to D. S. L.) and by National Institutes of Health Grant MH 48989 (to M. C. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- PCR
-
polymerase chain reaction
- MMTV
-
murine mammary tumor virus.
-
↵2 T. N. Sato and M. C. Wilson, unpublished observations.
