RGD Reference Report - Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions. - Rat Genome Database

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Structural basis for synaptic adhesion mediated by neuroligin-neurexin interactions.

Authors: Chen, X  Liu, H  Shim, AH  Focia, PJ  He, X 
Citation: Chen X, etal., Nat Struct Mol Biol. 2008 Jan;15(1):50-6. Epub 2007 Dec 16.
RGD ID: 11530522
Pubmed: PMID:18084303   (View Abstract at PubMed)
PMCID: PMC2922956   (View Article at PubMed Central)
DOI: DOI:10.1038/nsmb1350   (Journal Full-text)

The heterophilic synaptic adhesion molecules neuroligins and neurexins are essential for establishing and maintaining neuronal circuits by modulating the formation and maturation of synapses. The neuroligin-neurexin adhesion is Ca2+-dependent and regulated by alternative splicing. We report a structure of the complex at a resolution of 2.4 A between the mouse neuroligin-1 (NL1) cholinesterase-like domain and the mouse neurexin-1beta (NX1beta) LNS (laminin, neurexin and sex hormone-binding globulin-like) domain. The structure revealed a delicate neuroligin-neurexin assembly mediated by a hydrophilic, Ca2+-mediated and solvent-supplemented interface, rendering it capable of being modulated by alternative splicing and other regulatory factors. Thermodynamic data supported a mechanism wherein splicing site B of NL1 acts by modulating a salt bridge at the edge of the NL1-NX1beta interface. Mapping neuroligin mutations implicated in autism indicated that most such mutations are structurally destabilizing, supporting deficient neuroligin biosynthesis and processing as a common cause for this brain disorder.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nlgn1Ratcalcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules involved_inNAS PMID:18084303ComplexPortal 
Nrxn1Ratcalcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules involved_inNAS PMID:18084303ComplexPortal 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nlgn1Ratplasma membrane part_ofNAS PMID:18084303ComplexPortal 
Nrxn1Ratplasma membrane part_ofNAS PMID:18084303ComplexPortal 

Objects Annotated

Genes (Rattus norvegicus)
Nlgn1  (neuroligin 1)
Nrxn1  (neurexin 1)


Additional Information