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Papers In Press, published online ahead of print May 20, 2004
Molecular Biology, Westfälische Wilhelms-Universität Münster, Münster D-48149
Corresponding Author: apuschel{at}uni-muenster.de
The secreted semaphorin 3A is a member of a large family of proteins that act as guidance signals for axons and dendrites. While the receptors and signalling pathways that mediate the repulsive effects of semaphorins are beginning to be understood in some detail, the mechanisms that are responsible for the ability of Sema3A to stimulate the extension of dendrites remain to be elucidated. Here we show that PC12 cells, a model widely used to study neuronal differentiation, can be used to dissect this pathway. Sema3A is as effective as NGF in stimulating the extensions of neurites from PC12 cells. We show that Sema3A is able to regulate gene expression and identify mitochondria as a novel target of Sema3A signalling. Pharmacological block of mitochondrial reactive oxygen species production abolishes the extension of neurites in response to Sema3A. These results show that the characterization of transcripts that are regulated by axon guidance signals may help to identify novel components of their signalling pathways.
J. Biol. Chem, 10.1074/jbc.C400082200
Submitted on February 23, 2004
Revised on May 17, 2004
Accepted on May 20, 2004
Semaphorin 3A stimulates neurite extension and regulates gene expression in PC12 cells
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