Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms

Lu Chen, Dane M. Chetkovich, Ronald S. Petralia, Neal T. Sweeney, Yoshimi Kawasaki, Robert J. Wenthold, David S. Bredt, Roger A. Nicoll*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

835 Scopus citations

Abstract

Stargazer, an ataxic and epileptic mutant mouse, lacks functional AMPA (α-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.

Original languageEnglish (US)
Pages (from-to)936-943
Number of pages8
JournalNature
Volume408
Issue number6815
DOIs
StatePublished - Dec 21 2000

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms'. Together they form a unique fingerprint.

Cite this