PKC signaling mediates global enhancement of excitatory synaptogenesis in neurons triggered by local contact with astrocytes.
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.
Hama
Hiroshi
H
Laboratory for Cell Function Dynamics, Advanced Technology Development Group, Brain Science Institute, RIKEN, Wako-City, Saitama, Japan.
Hara
Chikako
C
Yamaguchi
Kazuhiko
K
Miyawaki
Atsushi
A
D000704:Analysis of Variance; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001253:Astrocytes / Q000502:physiology*; D002135:Calcium-Binding Proteins; D002273:Carcinogens / Q000494:pharmacology; D002452:Cell Count; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004622:Embryo, Mammalian; D005456:Fluorescent Dyes / Q000378:metabolism; D005959:Glucosidases; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins; D008845:Microinjections / Q000379:methods; D008967:Molecular Biology / Q000379:methods; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010455:Peptides / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D050857:Synaptotagmins; D013997:Time Factors; D014162:Transfection; D014178:Translocation, Genetic
D016718:Arachidonic Acid; D002135:Calcium-Binding Proteins; D002273:Carcinogens; D017077:Culture Media, Conditioned; D005456:Fluorescent Dyes; D005959:Glucosidases; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009419:Nerve Tissue Proteins; D010455:Peptides; D015240:Phorbol 12,13-Dibutyrate; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D011493:Protein Kinase C; D018091:Receptors, AMPA; D016708:Synaptophysin; D050857:Synaptotagmins; C512948:Prkcsh protein, rat; C033652:postsynaptic density proteins; C057986:echistatin