Annotated protein:Transmembrane protein 108 (Retrolinkin). Gene symbol: TMEM108. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q8BHE4
antibody wiki:
SynGO gene info:SynGO data @ TMEM108
Ontology domain:Biological Process
SynGO term:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0098696)
Synapse type(s):hippocampus, glutamatergic
Annotated paper:Jiao HF, et al. "Transmembrane protein 108 is required for glutamatergic transmission in dentate gyrus" Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):1177-1182 PMID:28096412
Figure(s):Figure 3, 4, S7
Annotation description:Figure 4c: TMEM108 puncta colabeled with GFP-GluA2 in spines and dendrites.

Figure 3: Abnormal Excitatory Transmission in Tmem108 MT DG Granule Neurons.
"The total excitatory charge transfer was decreased in MT mice compared with WT mice (Fig. 3B). However, the inhibitory synaptic charge was comparable (Fig. 3C). Consequently, the sEPSC/sIPSC ratio was decreased by almost 50% (Fig. 3D). To determine whether Tmem108 mutation altered evoked postsynaptic currents, we stimulated medial perforant pathway (MPP) with stimuli at gradually increasing intensity. As shown in Fig. 3 E-G, amplitudes of eEPSCs, but not eIPSCs, were reduced. These results suggest that the excitatory/inhibitory (E/I) balance was disrupted by Tmem108 mutation, mostly due to impaired excitatory synaptic activity."

Figure 4: Decreased AMPA Receptor Surface Level of Tmem108-Deficient DG Granule Neurons.
"Next, we stained neurons for endogenous GluA2 under permeabilizing and nonpermeabilizing conditions to assess total and surface AMPA receptors, respectively (21) (Fig. 4 D and E). Granule neurons were identified by Prox1 antibody. GluA2 staining was similar between permeabilized WT and MT granule neurons (Fig. 4D), indicating little change in total GluA2 level, in agreement with Western blot data (Fig. 4A). However, GluA2 staining was reduced in nonpermeabilized MT granule neurons, compared with that of WT (Fig. 4E). Quantitatively, reduction was observed in the number of GluA2 puncta, the puncta area, and soma GluA2 intensity (Fig. 4F), suggesting that Tmem108 may regulate GluA2 trafficking.

To test this hypothesis in the same neurons, we transfected GFP-GluA2 in granule cells. Surface GluA2 in live neurons was first labeled with chicken anti-GFP antibody (visualized by donkey anti-chicken antibody, red). Neurons were then fixed and stained with mouse anti-GFP antibody (visualized by goat anti-mouse antibody, green). As shown in Fig. S7 A and B, the GluA2 surface/total ratio was reduced in Tmem108 MT granule neurons, compared with WT neurons. These observations are in agreement with reduced eEPSC and mEPSC amplitudes in MT granule neurons. Together, these results suggest that Tmem108 promotes GluA2 surface expression, without changing total levels, and thus maintains spine morphology. This notion is supported by the observations that spine morphological deficits in Tmem108 MT DG neurons could be rescued by overexpressing GluA2 (Fig. 4 G and H)."

Authors conclude:
"Together, these results suggest that Tmem108 promotes GluA2 surface expression, without changing total levels, and thus maintains spine morphology. This notion is supported by the observations that spine morphological deficits in Tmem108 MT DG neurons could be rescued by overexpressing GluA2 (Fig. 4 G and H)."
Evidence tracking, Biological System:Intact tissue
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:5182
Dataset release (version):20231201
View annotation as GO-CAM model:Gene Ontology