Neurexin-neuroligin synaptic complex regulates schizophrenia-related DISC1/Kal-7/Rac1 "signalosome"

Sylwia Owczarek, Marie Louise Bang, Vladimir Berezin

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Article number167308
JournalNeural Plasticity
Volume2015
DOIs
Publication statusPublished - 2015

Fingerprint

Schizophrenia
Synaptic Membranes
Intracellular Membranes
Cell Adhesion Molecules
Synapses
Central Nervous System
Maintenance
Pathology
Brain
Genes
Proteins

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Neurexin-neuroligin synaptic complex regulates schizophrenia-related DISC1/Kal-7/Rac1 "signalosome". / Owczarek, Sylwia; Bang, Marie Louise; Berezin, Vladimir.

In: Neural Plasticity, Vol. 2015, 167308, 2015.

Research output: Contribution to journalArticle

@article{30cc1f27b98e464a85228e13529f02ea,
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.",
author = "Sylwia Owczarek and Bang, {Marie Louise} and Vladimir Berezin",
year = "2015",
doi = "10.1155/2015/167308",
language = "English",
volume = "2015",
journal = "Neural Plasticity",
issn = "2090-5904",
publisher = "Hindawi Publishing Corporation",

}

TY - JOUR

T1 - Neurexin-neuroligin synaptic complex regulates schizophrenia-related DISC1/Kal-7/Rac1 "signalosome"

AU - Owczarek, Sylwia

AU - Bang, Marie Louise

AU - Berezin, Vladimir

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84930965996&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930965996&partnerID=8YFLogxK

U2 - 10.1155/2015/167308

DO - 10.1155/2015/167308

M3 - Article

AN - SCOPUS:84930965996

VL - 2015

JO - Neural Plasticity

JF - Neural Plasticity

SN - 2090-5904

M1 - 167308

ER -