Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms.

Chen L, Chetkovich DM, Petralia RS, Sweeney NT, Kawasaki Y, Wenthold RJ, Bredt DS, Nicoll RA
Nature. 2000 408 (6815): 936-43

PMID: 11140673 · DOI:10.1038/35050030

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.

MeSH Terms (23)

Action Potentials Animals Calcium Calcium Channels Cerebellum COS Cells Disks Large Homolog 4 Protein Down-Regulation Excitatory Postsynaptic Potentials Glutamic Acid Guanylate Kinases Hippocampus Humans Intracellular Signaling Peptides and Proteins Membrane Proteins Mice Mice, Mutant Strains Nerve Tissue Proteins Neurons Protein Transport Receptors, AMPA Synapses Synaptic Membranes

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