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

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.

Pubmed ID: 11140673


  • Chen L
  • Chetkovich DM
  • Petralia RS
  • Sweeney NT
  • Kawasaki Y
  • Wenthold RJ
  • Bredt DS
  • Nicoll RA



Publication Data

January 3, 2001

Associated Grants


Mesh Terms

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