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Searching for Depolarization-Induced Genes that Modulate Synaptic Plasticity and Neurotrophin-Induced Genes that Mediate Neuronal Differentiation

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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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Authors and Affiliations

  1. Departments of Biological Chemistry. Pharmacology. Molecular Biology. Brain Research Institutes, UCLA, Los Angeles, CA, 90095

    Harvey R. Herschman

  2. Departments of Biological Chemistry. Molecular Biology. Brain Research Institutes, UCLA, Los Angeles, CA, 90095

    Gregory D. Ferguson

  3. Pediatrics. Brain Research Institutes, UCLA, Los Angeles, CA, 90095

    Jonathan D. Feldman

  4. Obstetrics and Gynecology. Molecular Biology, USA

    Robin Farias-Eisner

  5. Departments of Biological Chemistry. Molecular Biology. Brain Research Institutes, UCLA, Los Angeles, CA, 90095

    Linda Vician

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  1. Harvey R. Herschman
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  2. Gregory D. Ferguson
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  4. Robin Farias-Eisner
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  5. Linda Vician
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Herschman, H.R., Ferguson, G.D., Feldman, J.D. et al. Searching for Depolarization-Induced Genes that Modulate Synaptic Plasticity and Neurotrophin-Induced Genes that Mediate Neuronal Differentiation. Neurochem Res 25, 591–602 (2000). https://doi.org/10.1023/A:1007546600535

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