Semaphorin 3A stimulates neurite extension and regulates gene expression in PC12 cells.
The secreted semaphorin 3A (Sema3A) is a member of a large family of proteins that act as guidance signals for axons and dendrites. While the receptors and signaling 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 nerve growth factor in stimulating the extension of neurites from PC12 cells. We show that Sema3A is able to regulate gene expression and identify mitochondria as a novel target of Sema3A signaling. 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 signaling pathways.
Schwamborn
Jens C
JC
Institut für Allgemeine Zoologie und Genetik, Westfälische Wilhelms-Universität Münster, Schlossplatz 5, D-48149 Münster, Germany.
Fiore
Roberto
R
Bagnard
Dominique
D
Kappler
Joachim
J
Kaltschmidt
Christian
C
Püschel
Andreas W
AW
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D040121:Semaphorin-3A / Q000494:pharmacology*; D015398:Signal Transduction
D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D040121:Semaphorin-3A; D020932:Nerve Growth Factor