Molecular Organization of the Postsynaptic Specialization

• Published in: Proceedings of the National Academy of Sciences - PNAS 2001-06, Vol.98 (13), p.7058-7061
• Main Author: Sheng, Morgan
• Format: Article
• Language: English
• Subjects: AMPA receptors; Animals; Brain; Brain - physiology; Colloquium: Papers from the National Academy of Sciences Colloquium on Molecular Kinesis in Cellular Function and Plasticity; Dendritic spines; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials - physiology; Glutamate receptors; Molecular biology; N methyl D aspartate receptors; Nerve Tissue Proteins - physiology; Neurology; Neurons; Neuroscience; Physiological regulation; Proteins; Receptors; Receptors, AMPA - drug effects; Receptors, AMPA - physiology; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, N-Methyl-D-Aspartate - physiology; Synapses; Synapses - physiology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.111146298

A specific set of molecules including glutamate receptors is targeted to the postsynaptic specialization of excitatory synapses in the brain, gathering in a structure known as the postsynaptic density (PSD). Synaptic targeting of glutamate receptors depends on interactions between the C-terminal tails of receptor subunits and specific PDZ domain-containing scaffold proteins in the PSD. These scaffold proteins assemble a specialized protein complex around each class of glutamate receptor that functions in signal transduction, cytoskeletal anchoring, and trafficking of the receptors. Among the glutamate receptor subtypes, the N-methyl-D-aspartate receptor is relatively stably integrated in the PSD, whereas the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor moves in and out of the postsynaptic membrane in highly dynamic fashion. The distinctive cell biological behaviors of N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors can be explained by their differential interactions with cytoplasmic proteins.