Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms

Nature. 2000 Dec 21-28;408(6815):936-43. doi: 10.1038/35050030.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

  • CACNG2 protein, human
  • Cacng2 protein, mouse
  • Calcium Channels
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, AMPA
  • postsynaptic density proteins
  • Glutamic Acid
  • Guanylate Kinases
  • Calcium