PKC Signaling Mediates Global Enhancement of Excitatory Synaptogenesis in Neurons Triggered by Local Contact With Astrocytes

Neuron. 2004 Feb 5;41(3):405-15. doi: 10.1016/s0896-6273(04)00007-8.

Abstract

Here we provide evidence that astrocytes affect neuronal synaptogenesis by the process of adhesion. Local contact with astrocytes via integrin receptors elicited protein kinase C (PKC) activation in individual dissociated neurons cultured in astrocyte-conditioned medium. This activation, initially focal, soon spread throughout the entire neuron. We then demonstrated pharmacologically that the arachidonic acid cascade, triggered by the integrin reception, is responsible for the global activation of PKC. Local astrocytic contact also facilitated excitatory synaptogenesis throughout the neuron, a process which could be blocked by inhibitors of both integrins and PKC. Thus, propagation of PKC signaling represents an underlying mechanism for global neuronal maturation following local astrocyte adhesion.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Arachidonic Acid / pharmacology
  • Astrocytes / physiology*
  • Calcium-Binding Proteins*
  • Carcinogens / pharmacology
  • Cell Count
  • Cells, Cultured
  • Coculture Techniques
  • Culture Media, Conditioned / pharmacology
  • Embryo, Mammalian
  • Fluorescent Dyes / metabolism
  • Glucosidases
  • Hippocampus / cytology
  • Immunohistochemistry / methods
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins*
  • Membrane Glycoproteins / metabolism
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Proteins*
  • Microinjections / methods
  • Molecular Biology / methods
  • Myristoylated Alanine-Rich C Kinase Substrate
  • Nerve Tissue Proteins / metabolism
  • Neurons / physiology*
  • Patch-Clamp Techniques / methods
  • Peptides / pharmacology
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Platelet Aggregation Inhibitors / pharmacology
  • Protein Kinase C / physiology*
  • Rats
  • Rats, Wistar
  • Receptors, AMPA / metabolism
  • Signal Transduction / physiology*
  • Synapses / drug effects
  • Synapses / physiology*
  • Synaptophysin / metabolism
  • Synaptotagmins
  • Time Factors
  • Transfection
  • Translocation, Genetic

Substances

  • Calcium-Binding Proteins
  • Carcinogens
  • Culture Media, Conditioned
  • Fluorescent Dyes
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Peptides
  • Phosphoproteins
  • Platelet Aggregation Inhibitors
  • Prkcsh protein, rat
  • Receptors, AMPA
  • Synaptophysin
  • postsynaptic density proteins
  • echistatin
  • Myristoylated Alanine-Rich C Kinase Substrate
  • Synaptotagmins
  • Arachidonic Acid
  • Phorbol 12,13-Dibutyrate
  • Protein Kinase C
  • Glucosidases
  • glutamate receptor ionotropic, AMPA 1