|Annotated protein:||Neurexin-1 (Neurexin I-alpha) (Neurexin-1-alpha). Gene symbol: NRXN1. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q9CS84|
|SynGO gene info:||SynGO data @ NRXN1|
|Ontology domain:||Biological Process|
|SynGO term:||synapse assembly (GO:0007416)|
|Synapse type(s):||hippocampus, glutamatergic|
|Annotated paper:||Roppongi RT, et al. "LRRTMs Organize Synapses through Differential Engagement of Neurexin and PTPsigma" Neuron. 2020 Apr 8;106(1):108-125.e12 PMID:31995730|
|Figure(s):||Figs 5, 6 and 8 (J-K)|
|Annotation description:||*It is known that neurexins (Nrxs) proteins participate in the synapse assembly process (we can find some related SynGo annotations for Nrx1-alfa (ID 894) / beta (ID900)) and one of their postsynaptic ligands are LRRTMs proteins. In this paper, it is shown that Nrx1-gamma is a novel presynaptic organizer and interacts with LRRTM3/4 through the heparan sulfate (HS) Nrx domain.|
-In Fig 5 (D-E), we can observe in hippocampal neurons how LRRTM4 binds to Nrx1-gamma but not to Nrx1-gamma with the HS site at serine 316 mutated to alanine (indicated like 'delta-HS' in the paper).
In Fig 5 (G-H) using a COS7-neuron co-culture assay with a silencing for Nrxs (shNrx neurons), it is determined that the overexpression of Nrx1-gamma restores the synaptogenic activity of LRRTM3 and 4, but not LRRTM1 and 2, which is observed through of a higher Synapsin clustering.
Also, in Fig 5F it is shown a co-immunoprecipitation of LRRTM4/3 with Nrx1-gamma (in absence of heparinase treatment) indicating the role of this Nrx1 as an endogenous transsynaptic partner.
In Fig 6, it is suggested a reduction in the number of excitatory synapse in dentate gyrus granule cells (where LRRTM3/4 are highly located) with Nrx1-gamma silenced.
-In Fig 8 (J-K), we can see in an 'in vivo' model how the disruption of LRRTM4-Nrxs interaction alters the synaptic function. In this case, they use a knockin mouse mimic Mutation5 (described in Fig2 of this paper, it consists of the mutation of 2 residues of arginine and lysine to alanine for LRRTM4 sequence and results in an alteration of LRRTM4-NRxs binding through HS site).
From synaptosomes of this Lrrtm4 RK-RI mouse, they observe a lower LRRTM4-Nrxs co-immunoprecipitation (for alfa, beta, and gamma) than in WT mice.
In Fig 5A and FigS5, it is shown that Nrx1-gamma has an HS modification site like alfa/beta transcripts and that this protein is expressed in the neuronal surface.
|Evidence tracking, Biological System:||Intact tissue|
|Evidence tracking, Protein Targeting:||Genetic transformation (eg; knockout, knockin, mutations)|
RNAi / shRNA
|Evidence tracking, Experiment Assay:||Wide-field fluorescence|
Whole-cell patch clamp
IP + WB/MSMS
|Annotator(s):||Carlos Pascual-Caro (ORCID:0000-0002-2345-393X)|
Anjali Amrapali Vishwanath (ORCID:0000-0002-9888-0928)
Jaime de Juan-Sanz (ORCID:0000-0002-1212-5623)
|Lab:||ICM - Brain and Spine Institute, Hpital Piti Salptrire, 47 Boulevard de l'Hpital, 75013 Paris, France|
|Additional literature:||In this paper, it is shown that neurons lacking heparan sulfate domain on Neurexins present alterations in the binding of neurexins to postsynaptic ligands like LRRTMs and Neuroglins proteins, damaging or altering the synaptic function. @ PMID:30100184|
|SynGO annotation ID:||4049|
|Dataset release (version):||20210225|
|View annotation as GO-CAM model:|