Abstract
Stargazer, an ataxic and epileptic mutant mouse, lacks functional AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate) receptors on cerebellar granule cells. Stargazin, the mutated protein, interacts with both AMPA receptor subunits and synaptic PDZ proteins, such as PSD-95. The interaction of stargazin with AMPA receptor subunits is essential for delivering functional receptors to the surface membrane of granule cells, whereas its binding with PSD-95 and related PDZ proteins through a carboxy-terminal PDZ-binding domain is required for targeting the AMPA receptor to synapses. Expression of a mutant stargazin lacking the PDZ-binding domain in hippocampal pyramidal cells disrupts synaptic AMPA receptors, indicating that stargazin-like mechanisms for targeting AMPA receptors may be widespread in the central nervous system.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Action Potentials
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Animals
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COS Cells
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Calcium / metabolism
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Calcium Channels / genetics*
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Calcium Channels / physiology
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Cerebellum / metabolism
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Disks Large Homolog 4 Protein
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Down-Regulation
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Excitatory Postsynaptic Potentials
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Glutamic Acid / metabolism
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Guanylate Kinases
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Hippocampus / cytology
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Hippocampus / metabolism
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Humans
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Mice
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Mice, Mutant Strains
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Nerve Tissue Proteins / metabolism
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Neurons / metabolism
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Protein Transport
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Receptors, AMPA / metabolism*
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Synapses / metabolism*
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Synaptic Membranes / metabolism
Substances
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CACNG2 protein, human
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Cacng2 protein, mouse
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Calcium Channels
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Disks Large Homolog 4 Protein
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Dlg4 protein, mouse
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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Receptors, AMPA
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postsynaptic density proteins
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Glutamic Acid
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Guanylate Kinases
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Calcium