title: Neurexin-Neuroligin Synaptic Complex Regulates Schizophrenia-Related DISC1/Kal-7/Rac1 "Signalosome".
abstract: Neurexins (NXs) and neuroligins (NLs) are cell adhesion molecules that are localized at opposite sites of synaptic membranes. They interact with each other to promote the assembly, maintenance, and function of synapses in the central nervous system. Both NX and NL are cleaved from a membrane-attached intracellular domain in an activity-dependent manner, generating the soluble ectodomain of NX or NL. Expression of the NX1 and NX3 genes in the brain appears to be regulated by a schizophrenia-related protein, DISC1. Here, we show that soluble ecto-NX1β can regulate the expression of DISC1 and induce signaling downstream of DISC1. We also show that NL1 binds to a well-characterized DISC1 interaction partner, Kal-7, and this interaction can be compromised by DISC1. Our results indicate that the NX/NL synaptic complex is intrinsically involved in the regulation of DISC1 function, thus contributing to a better understanding of the pathology of schizophrenia.
authors.affiliation: Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, 2200 Copenhagen, Denmark ; Research Laboratory for Stereology and Neuroscience, Bispebjerg Hospital, 2400 Copenhagen, Denmark.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Owczarek
authors.affiliation: Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Marie Louise
authors.initials: ML
authors.lastname: Bang
authors.affiliation: Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Berezin
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017208:Rats, Wistar; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C412476:DISC1 protein, human; D020662:Guanine Nucleotide Exchange Factors; D009419:Nerve Tissue Proteins; C107953:RAC1 protein, human; C093438:neuroligin 1; C086959:neurexin Ibeta; C503866:KALRN protein, human; D017346:Protein Serine-Threonine Kinases; D020830:rac1 GTP-Binding Protein