RGD Reference Report - Neuroligin-1 performs neurexin-dependent and neurexin-independent functions in synapse validation. - Rat Genome Database

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Neuroligin-1 performs neurexin-dependent and neurexin-independent functions in synapse validation.

Authors: Ko, J  Zhang, C  Arac, D  Boucard, AA  Brunger, AT  Sudhof, TC 
Citation: Ko J, etal., EMBO J. 2009 Oct 21;28(20):3244-55. doi: 10.1038/emboj.2009.249. Epub 2009 Sep 3.
RGD ID: 8554379
Pubmed: PMID:19730411   (View Abstract at PubMed)
PMCID: PMC2771087   (View Article at PubMed Central)
DOI: DOI:10.1038/emboj.2009.249   (Journal Full-text)

Postsynaptic neuroligins are thought to perform essential functions in synapse validation and synaptic transmission by binding to, and dimerizing, presynaptic alpha- and beta-neurexins. To test this hypothesis, we examined the functional effects of neuroligin-1 mutations that impair only alpha-neurexin binding, block both alpha- and beta-neurexin binding, or abolish neuroligin-1 dimerization. Abolishing alpha-neurexin binding abrogated neuroligin-induced generation of neuronal synapses onto transfected non-neuronal cells in the so-called artificial synapse-formation assay, even though beta-neurexin binding was retained. Thus, in this assay, neuroligin-1 induces apparent synapse formation by binding to presynaptic alpha-neurexins. In transfected neurons, however, neither alpha- nor beta-neurexin binding was essential for the ability of postsynaptic neuroligin-1 to dramatically increase synapse density, suggesting a neurexin-independent mechanism of synapse formation. Moreover, neuroligin-1 dimerization was not required for either the non-neuronal or the neuronal synapse-formation assay. Nevertheless, both alpha-neurexin binding and neuroligin-1 dimerization were essential for the increase in apparent synapse size that is induced by neuroligin-1 in transfected neurons. Thus, neuroligin-1 performs diverse synaptic functions by mechanisms that include as essential components of alpha-neurexin binding and neuroligin dimerization, but extend beyond these activities.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nlgn1Ratpositive regulation of excitatory postsynaptic potential involved_inIDA PMID:19730411BHF-UCL 
Nlgn1Ratpositive regulation of synaptic transmission, glutamatergic involved_inIDA PMID:19730411BHF-UCL 
Nlgn1Ratpresynaptic membrane assembly involved_inIDA PMID:19730411BHF-UCL 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nlgn1Ratcell surface located_inIDA PMID:19730411BHF-UCL 
BsnRatexcitatory synapse located_inIDA PMID:19730411BHF-UCL 
Dlg4Ratexcitatory synapse located_inIDA PMID:19730411BHF-UCL 
Gria1Ratexcitatory synapse located_inIDA PMID:19730411BHF-UCL 
Grin1Ratexcitatory synapse located_inIDA PMID:19730411BHF-UCL 
Nlgn1Ratexcitatory synapse located_inICGO:2000463PMID:19730411BHF-UCL 
Rab3gap1Ratexcitatory synapse located_inIDA PMID:19730411BHF-UCL 
Slc17a7Ratexcitatory synapse located_inIDA PMID:19730411BHF-UCL 
SypRatexcitatory synapse located_inIDA PMID:19730411BHF-UCL 
Syt1Ratexcitatory synapse located_inIDA PMID:19730411BHF-UCL 
Unc13aRatexcitatory synapse located_inIDA PMID:19730411BHF-UCL 

Molecular Function

  

Objects Annotated

Genes (Rattus norvegicus)
Bsn  (bassoon (presynaptic cytomatrix protein))
Dlg4  (discs large MAGUK scaffold protein 4)
Gria1  (glutamate ionotropic receptor AMPA type subunit 1)
Grin1  (glutamate ionotropic receptor NMDA type subunit 1)
Nlgn1  (neuroligin 1)
Nrxn1  (neurexin 1)
Rab3gap1  (RAB3 GTPase activating protein catalytic subunit 1)
Slc17a7  (solute carrier family 17 member 7)
Syp  (synaptophysin)
Syt1  (synaptotagmin 1)
Unc13a  (unc-13 homolog A)


Additional Information