Molecular reconstitution of functional GABAergic synapses with expression of neuroligin-2 and GABAA receptors

Mol Cell Neurosci. 2007 May;35(1):14-23. doi: 10.1016/j.mcn.2007.01.013. Epub 2007 Jan 30.

Abstract

Trans-synaptic cell adhesion molecules neuroligins and neurexins play an important role in promoting central synapse formation. We report here a molecular reconstruction of functional GABAergic synapses in non-neuronal cells with the coexpression of postsynaptic cell adhesion molecule neuroligin-2 (NL-2) and GABA(A) receptors. HEK 293T cells were co-transfected with GABA(A) receptors and NL-2 or its homologue neuroligin-1 (NL-1), and then cocultured with hypothalamic cultures which are enriched with GABAergic neurons. Both spontaneous and action potential-evoked GABAergic events were readily detected in HEK 293T cells coexpressing GABA(A) receptors with NL-2, but not with NL-1. Aggregating NL-2 with specific antibodies in live cells resulted in coaggregation of GABA(A) receptors. Expression of NL-2 in HEK 293T cells also induced stronger GABAergic presynaptic differentiation than that of NL-1 in neuronal cocultures. These results suggest that NL-2 may potentially serve as a central organizer for GABAergic synapse assembly by interacting with both presynaptic neurexins and postsynaptic GABA(A) receptors.

Publication types

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

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal
  • Cells, Cultured
  • Gene Expression
  • Humans
  • Hypothalamus, Middle / cytology
  • Inhibitory Postsynaptic Potentials / physiology
  • Kidney / cytology
  • Kinetics
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Patch-Clamp Techniques
  • Presynaptic Terminals / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / physiology*
  • Transfection
  • gamma-Aminobutyric Acid / physiology*

Substances

  • Cell Adhesion Molecules, Neuronal
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, GABA-A
  • neuroligin 2
  • gamma-Aminobutyric Acid