Searching for depolarization-induced genes that modulate synaptic plasticity and neurotrophin-induced genes that mediate neuronal differentiation.
We identify and characterize two classes of immediate-early genes: (i) genes, induced by depolarization in neurons, that play a role in depolarization-induced neuronal plasticity and (ii) genes, induced in neuronal precursors by neurotrophins, that play a causal role in neurotrophin-directed neuronal differentiation. We use rat PC12 pheochromocytoma cells to identify (i) genes preferentially induced by [depolarization or forskolin] versus [Nerve Growth Factor (NGF) or Epidermal Growth Factor (EGF)] and (ii) genes preferentially induced by NGF versus EGF. We describe (i) a collection of genes preferentially induced by depolarization/forskolin in PC12 cells and by kainic acid in vivo, and (ii) a collection of genes preferentially induced by NGF. The synaptotagmin IV gene encodes a synaptic vesicle protein whose level is modulated by depolarization. NGF preferentially induces the urokinase-plasminogen activator receptor in PC12 cells. Antisense oligonucleotide and anti-UPAR antibody experiments demonstrate that NGF-induced UPAR expression is required for NGF-driven PC12 cell differentiation.
Herschman
H R
HR
Department of Biological Chemistry, UCLA, Los Angeles, CA 90095, USA. hherschman@mednet.ucla.edu
Ferguson
G D
GD
Feldman
J D
JD
Farias-Eisner
R
R
Vician
L
L
D000310:Adrenal Gland Neoplasms; D000818:Animals; D002454:Cell Differentiation; D005576:Colforsin / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D017781:Genes, Immediate-Early / Q000187:drug effects / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D016716:PC12 Cells; D010673:Pheochromocytoma; D051381:Rats; D013569:Synapses / Q000502:physiology*
D009414:Nerve Growth Factors; D005576:Colforsin; D004815:Epidermal Growth Factor; D007608:Kainic Acid