Neurologin function in excitatory and inhibitory synapses

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Title: Neurologin function in excitatory and inhibitory synapses
Author: Zang, Tong
Abstract: Neuroligins (NLs ) are postsynaptic cell adhesion molecules which by binding to presynaptic neurexins (NRXs ) are thought to mediate synapse formation and function . Both NLs and NRXs are discussed in the genetic correlation to Autism . Over -expression of NLs could induce the formation of synaptic contacts with axons in non -neuronal cells and increase the synaptic density and response in cultured neurons , through binding and recruiting NRXs ; however , little is known about NL signaling though NRXs or inside the cell . First , we hypothesized that NLs signal through their cytoplasmic region . Over -expression of NL1 with cytoplasmic tail truncation abolished the increase of synaptic density by NL1 full length . By yeast two hybrid screening using NL2 cytoplasmic region , we identified potential interaction partners , of which Necab2 and NRP /B (also named as ectodermal cortex 1 , EC1 ) are two promising candidates and the interactions were confirmed . NL1 or NL2 c -tail truncations partially abolished the change in miniature IPSC , but not the evoked responses . NL c -tail binding partners ?ver -expression does not show any change in evoked responses . It suggested that NL cytoplasmic region is important for some neuronal changes but does not contribute to the major phenotype of NLs . And we investigated the contribution of NL -NRX binding by using NL extracellular NRX binding mutants . The mutants abolished the change of the evoked and miniature inhibitory responses from the NL2 wild type , which suggested the inhibitory responses triggered by NL2 go through NRXs . And the slight change of the paired pulse ratio suggested the change of presynaptic calcium through binding . The study suggested that NL2 facilitate the inhibitory synaptic transmission through extracellular region via neurexin binding , possibly by the increase in presynaptic calcium . We also found Brain -specific Angiogenesis Inhibitors (BAIs ) , a family of G -protein coupled receptors (GPCRs ) , will bind to NLs extracellularly and may serve as signaling modules binding to NLs . Over -expression of BAIs do not change evoked IPSCs , but Bai1 decreased evoked EPSCs and increased the burst duration in the spontaneous responses , possibly because of some secondary responses . Therefore , we found NL -NRX though NL extracellular region is important for NL2 function in synaptic transmission , and BAIs may be potential signaling molecules of NLs
URI: http : / /hdl .handle .net /2152 .5 /557
Date: 2008-09-19


Neurologin function in excitatory and inhibitory synapses. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /557 .

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