RGD Reference Report - SALM4 suppresses excitatory synapse development by cis-inhibiting trans-synaptic SALM3-LAR adhesion. - Rat Genome Database

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SALM4 suppresses excitatory synapse development by cis-inhibiting trans-synaptic SALM3-LAR adhesion.

Authors: Lie, Eunkyung  Ko, Ji Seung  Choi, Su-Yeon  Roh, Junyeop Daniel  Cho, Yi Sul  Noh, Ran  Kim, Doyoun  Li, Yan  Kang, Hyeyeon  Choi, Tae-Yong  Nam, Jungyong  Mah, Won  Lee, Dongmin  Lee, Seong-Gyu  Kim, Ho Min  Kim, Hyun  Choi, Se-Young  Um, Ji Won  Kang, Myoung-Goo  Bae, Yong Chul  Ko, Jaewon  Kim, Eunjoon 
Citation: Lie E, etal., Nat Commun. 2016 Aug 2;7:12328. doi: 10.1038/ncomms12328.
RGD ID: 13702184
Pubmed: PMID:27480238   (View Abstract at PubMed)
PMCID: PMC4974644   (View Article at PubMed Central)
DOI: DOI:10.1038/ncomms12328   (Journal Full-text)

Synaptic adhesion molecules regulate various aspects of synapse development, function and plasticity. These functions mainly involve trans-synaptic interactions and positive regulations, whereas cis-interactions and negative regulation are less understood. Here we report that SALM4, a member of the SALM/Lrfn family of synaptic adhesion molecules, suppresses excitatory synapse development through cis inhibition of SALM3, another SALM family protein with synaptogenic activity. Salm4-mutant (Salm4(-/-)) mice show increased excitatory synapse numbers in the hippocampus. SALM4 cis-interacts with SALM3, inhibits trans-synaptic SALM3 interaction with presynaptic LAR family receptor tyrosine phosphatases and suppresses SALM3-dependent presynaptic differentiation. Importantly, deletion of Salm3 in Salm4(-/-) mice (Salm3(-/-); Salm4(-/-)) normalizes the increased excitatory synapse number. These results suggest that SALM4 negatively regulates excitatory synapses via cis inhibition of the trans-synaptic SALM3-LAR adhesion.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Lrfn3Ratregulation of presynapse assembly involved_inIDA PMID:27480238SynGO 
Lrfn3Ratregulation of presynapse assembly involved_inIMP PMID:27480238SynGO 
Lrfn3Ratregulation of synaptic membrane adhesion involved_inIDA PMID:27480238SynGO 
Lrfn3Ratregulation of synaptic membrane adhesion involved_inIMP PMID:27480238SynGO 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Lrfn3Ratglutamatergic synapse is_active_inIDA PMID:27480238SynGO 
Lrfn3Ratglutamatergic synapse is_active_inIMP PMID:27480238SynGO 
Lrfn3Ratpostsynaptic density membrane is_active_inIDA PMID:27480238SynGO 
Lrfn3Ratpostsynaptic density membrane is_active_inIEP PMID:27480238SynGO 

Objects Annotated

Genes (Rattus norvegicus)
Lrfn3  (leucine rich repeat and fibronectin type III domain containing 3)


Additional Information