PubMed 11140673

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

Authors: L Chen, D M Chetkovich, R S Petralia, N T Sweeney, Y Kawasaki, R J Wenthold, D S Bredt, R A Nicoll

Journal, date & volume: Nature, 2000 Dec 21-28 , 408, 936-43

PubMed link:

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.