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A New Regulatory Mechanism for Synaptic Transmission Is Clarified
Laboratory for Memory and Learning |
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Researchers Dr. Hirokazu Hirai and Dr. Shinji Matsuda of the Laboratory for Memory and Learning (Head, Dr. Masao Ito) have elucidated the glutamate receptor clustering mechanism which is regarded as being involved in the plasticity of the brain.
The glutamate receptor is distributed widely in mammal brains and forms dense clusters, that are localized in the excitatory postsynaptic membrane. This creates an efficient neuro-transmission environment at the synapse. This transmission efficiency can be varied by either making the glutamate receptor clusters denser or by destroying them, and this mechanism is one that is attracting attention as a means of describing the plasticity of the brain.
The recent discoveries have demonstrated that the clustering of AMPA type and ƒÂ-type glutamate receptors is regulated by phosphorylation and the presence of calcium, respectively. This was based on our discovery that when a serine residue at the intracellular carboxyl terminus of the AMPA receptor is phosphorylated by protein kinase C or when the intracellular calcium in the vicinity of a ƒÂ-receptor increases, the linkage between the receptor and the protein which fixes it is lost and the cluster is destroyed.
An increase in the intracellular calcium or the activation of PKC occurs as a result of a variety of synaptic activities. Consequently, the transmission efficiency of the synapse and its plasticity are controlled via modulation of the density of the receptors in the postsynaptic membrane, which are regulated by the mechanism described above.
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- Matsuda, S., Mikawa, S., Hirai, H.
Phosphorylation of serine-880 in GluR2 by protein kinase C prevents its C-terminus from binding with glutamate receptor interacting protein.
J. Neurochem. (1999)
- Hirai, H., Matsuda, S.
Interaction of the C-terminal domain of dglutamate receptor with spectrin in the dendritic spines of cultured Purkinje cells.
Neurosci. Res. (1999)
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The ƒÂ-type glutamate receptor is fixed on the actin filament via spectrin. When the calcium increases, the linkage between the receptor and the spectrin is disconnected and the receptor is separated from the synapse.
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