Molecular reconstitution of functional GABAergic synapses with expression of neuroligin-2 and GABAA receptors.
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.
Dong
Ning
N
Department of Biology, The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
Qi
Jinshun
J
Chen
Gong
G
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D007033:Hypothalamus, Middle / Q000166:cytology; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D007668:Kidney / Q000166:cytology; D007700:Kinetics; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; C098003:neuroligin 2; D005680:gamma-Aminobutyric Acid