Learning from stargazin: the mouse, the phenotype and the unexpected

Curr Opin Neurobiol. 2006 Jun;16(3):275-80. doi: 10.1016/j.conb.2006.04.002. Epub 2006 May 5.

Abstract

The stargazin gene (also referred to as Cacng2) has been identified by forward genetics in a spontaneous mouse mutant with ataxic gait, upward head-elevating movements (hence the name stargazer for the mouse) and episodes of spike-wave discharges. Stargazin is related to the gamma-1 subunit of skeletal muscle voltage-dependent calcium channel (VDCC), and a deficit in its role as auxiliary VDCC subunit was proposed to underlie the epileptic phenotype of the mouse; yet, a conclusive demonstration of stargazin function in VDCC regulation is still lacking. In contrast, stargazin and its three closely related isoforms gamma-3, gamma-4 and gamma-8 were shown to function as auxiliary subunits for a very different ion channel - the AMPA-type glutamate receptor - prominently regulating early intracellular transport, synaptic targeting and anchoring, and ion channel functions of this major excitatory receptor in the brain.

Publication types

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

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / physiopathology
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Mice
  • Mice, Neurologic Mutants
  • Phenotype
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Protein Transport / genetics
  • Receptors, AMPA / genetics
  • Receptors, AMPA / metabolism*
  • Synapses / genetics
  • Synapses / metabolism*
  • Synaptic Transmission / genetics*

Substances

  • Cacng2 protein, mouse
  • Calcium Channels
  • Protein Isoforms
  • Protein Subunits
  • Receptors, AMPA