Searching for Depolarization-Induced Genes that Modulate Synaptic Plasticity and Neurotrophin-Induced Genes that Mediate Neuronal Differentiation |
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| Authors: | Herschman Harvey R. Ferguson Gregory D. Feldman Jonathan D. Farias-Eisner Robin Vician Linda |
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| Affiliation: | (1) Departments of Biological Chemistry. Pharmacology. Molecular Biology. Brain Research Institutes, UCLA, Los Angeles, CA, 90095;(2) Departments of Biological Chemistry. Molecular Biology. Brain Research Institutes, UCLA, Los Angeles, CA, 90095;(3) Pediatrics. Brain Research Institutes, UCLA, Los Angeles, CA, 90095;(4) Obstetrics and Gynecology. Molecular Biology, USA;(5) Departments of Biological Chemistry. Molecular Biology. Brain Research Institutes, UCLA, Los Angeles, CA, 90095 |
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| Abstract: | 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. |
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| Keywords: | Depolarization forskolin nerve growth factor synaptotagmin UPAR PC12 cells |
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