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Mol Cell Neurosci. 2007 May;35(1):14-23. Epub 2007 Jan 30.

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

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Department of Biology, The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.


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.

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