title: Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms.
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.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143, USA.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: D M
authors.initials: DM
authors.lastname: Chetkovich
authors.forename: R S
authors.initials: RS
authors.lastname: Petralia
authors.forename: N T
authors.initials: NT
authors.lastname: Sweeney
authors.forename: Y
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: R J
authors.initials: RJ
authors.lastname: Wenthold
authors.forename: D S
authors.initials: DS
authors.lastname: Bredt
authors.forename: R A
authors.initials: RA
authors.lastname: Nicoll
mesh_terms: D000200:Action Potentials; D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics* / Q000502:physiology; D002531:Cerebellum / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D015536:Down-Regulation; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000378:metabolism; D051528:Guanylate Kinases; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D021381:Protein Transport; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism
chemical_list: C491912:CACNG2 protein, human; C113940:Cacng2 protein, mouse; D015220:Calcium Channels; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; C033652:postsynaptic density proteins; D018698:Glutamic Acid; D051528:Guanylate Kinases; D002118:Calcium