title: Specific trans-synaptic interaction with inhibitory interneuronal neurexin underlies differential ability of neuroligins to induce functional inhibitory synapses.
abstract: Synaptic transmission depends on the matching and alignment of presynaptically released transmitters and postsynaptic neurotransmitter receptors. Neuroligin (NL) and Neurexin (Nrxn) proteins are trans-synaptic adhesion molecules that are important in validation and maturation of specific synapses. NL isoforms NL1 and NL2 have specific functional roles in excitatory and inhibitory synapses, respectively, but the molecular basis behind this distinction is still unclear. We show here that the extracellular domain of NL2 confers its unique ability to enhance inhibitory synaptic function when overexpressed in rat hippocampal pyramidal neurons, whereas NL1 normally only promotes excitatory synapses. This specificity is conferred by presynaptic Nrxn isoforms, as NL1 can also induce functional inhibitory synapse connections when the presynaptic interneurons ectopically express an Nrxn isoform that binds to NL1. Our results indicate that trans-synaptic interaction with differentially expressed presynaptic Nrxns underlies the distinct functions of NL1 and NL2, and is sufficient to induce functional inhibitory synapse formation.
authors: Department of Psychiatry, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01604, USA. Kensuke.Futai@umassmed.edu
authors: Kensuke
authors: K
authors: Futai
authors: Christopher D
authors: CD
authors: Doty
authors: Brian
authors: B
authors: Baek
authors: Jubin
authors: J
authors: Ryu
authors: Morgan
authors: M
authors: Sheng
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D057809:HEK293 Cells; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007395:Interneurons / Q000378:metabolism* / Q000502:physiology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D020033:Protein Isoforms / Q000378:metabolism / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism* / Q000502:physiology; D013569:Synapses / Q000378:metabolism / Q000502:physiology*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D009419:Nerve Tissue Proteins; C547193:Nrxn1 protein, rat; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; C093438:neuroligin 1; C098003:neuroligin 2