Gephyrin-independent clustering of postsynaptic GABA(A) receptor subtypes

Mol Cell Neurosci. 2001 Jun;17(6):973-82. doi: 10.1006/mcne.2001.0983.


Gephyrin has been shown to be essential for the synaptic localization of the inhibitory glycine receptor and major GABA(A) receptor (GABA(A)R) subtypes. However, in retina certain GABA(A)R subunits are found at synaptic sites in the absence of gephyrin. Here, we quantitatively analyzed GABA(A)R alpha1, alpha2, alpha3, alpha5, beta2/3, and gamma2 subunit immunoreactivities in spinal cord sections derived from wild-type and gephyrin-deficient (geph -/-) mice. The punctate staining of GABA(A)R alpha1 and alpha5 subunits was unaltered in geph -/- mice, whereas the numbers of alpha2-, alpha3-, beta2/3-, and gamma2-subunit-immunoreactive synaptic sites were significantly or even strikingly reduced in the mutant animals. Immunostaining with an antibody specific for the vesicular inhibitory amino acid transporter revealed that the number of inhibitory presynaptic terminals is unaltered upon gephyrin deficiency. These data show that in addition to gephyrin other clustering proteins must exist that mediate the synaptic localization of selected GABA(A)R subtypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems*
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Differentiation / genetics*
  • Fetus
  • Gene Expression Regulation, Developmental / physiology
  • Immunohistochemistry
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics
  • Mice
  • Mice, Knockout
  • Neural Inhibition / genetics*
  • Neuronal Plasticity / genetics
  • Neurons / cytology
  • Neurons / metabolism*
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / ultrastructure
  • Receptors, GABA-A / metabolism*
  • Spinal Cord / cytology
  • Spinal Cord / embryology*
  • Spinal Cord / metabolism
  • Synaptic Membranes / metabolism*
  • Synaptic Membranes / ultrastructure
  • Vesicular Inhibitory Amino Acid Transport Proteins


  • Amino Acid Transport Systems
  • Carrier Proteins
  • Membrane Proteins
  • Receptors, GABA-A
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • Viaat protein, mouse
  • gephyrin