Annotated protein:Neuroligin-4, X-linked (Neuroligin X) (HNLX). Gene symbol: NLGN4X. Taxonomy: Homo sapiens (Human). Uniprot ID: Q8N0W4
antibody wiki:
SynGO gene info:SynGO data @ NLGN4X
Ontology domain:Biological Process
SynGO term:regulation of synapse assembly (GO:0051963)
Annotated paper:Marro SG, et al. "Neuroligin-4 Regulates Excitatory Synaptic Transmission in Human Neurons" Neuron. 2019 Aug 21;103(4):617-626.e6 PMID:31257103
Figure(s):Figure 2
Annotation description:"Neuroligins are adhesion proteins of the postsynaptic membrane (Graf et al., 2004, Song et al., 1999)" (PMID:15620359, PMID:9927700)

The Human NLGN4 gene is quite distinct from Mouse NLGN4 ("Nlgn4-like") and e.g. absent from Rat genome (Figure 1a). In this study, Human embryonic stem cells (ESCs) were differentiated into excitatory neurons (iN cells) with dorsal forebrain characteristics by expressing the transcription factor Ngn2 (Ngn2 iN cells). These are devoid of NLGN4 protein (Figure 1E) and thus used to assess the effect of NLGN4 gain of function.

5 weeks after transducing NLGN4 into these cells, authors found more Synapsin1/Homer1-positive puncta along dendrites than control neurons whereas puncta intensity and size were unchanged, suggesting that NLGN4 overexpression increased synapse numbers (Figures 2B and S2A).

However, electrophysiological recordings showed that NLGN4 overexpression decreased the frequency (but not amplitude) of spontaneous excitatory postsynaptic currents (sEPSCs), which represent mostly miniature EPSCs in these type of cultures, i.e., non-action potential triggered synaptic transmission (Figure 2C; Zhang et al., 2013).

Moreover, NLGN4 overexpression decreased the amplitude of action potential-triggered synaptic transmission (Figure 2D).

Authors concluded that "These experiments suggest that NLGN4 overexpressed induced the formation of new synapses, but simultaneously decreased the fraction of synapses that are functional"
Evidence tracking, Biological System:Cultured neurons
Evidence tracking, Protein Targeting:Genetic transformation (eg; knockout, knockin, mutations)
Over-expression
Evidence tracking, Experiment Assay:Whole-cell patch clamp
Confocal
Annotator(s):Frank Koopmans (ORCID:0000-0002-4973-5732)
Guus Smit (ORCID:0000-0002-2286-1587)
Matthijs Verhage (ORCID:0000-0002-2514-0216)
Lab:Department of Functional Genomics, Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
SynGO annotation ID:5003
Dataset release (version):20231201
View annotation as GO-CAM model:Gene Ontology