| Annotated protein: | Guanine nucleotide exchange factor C9orf72. Gene symbol: C9ORF72. Taxonomy: Homo sapiens (Human). Uniprot ID: Q96LT7 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ C9ORF72 |
| Ontology domain: | Cellular Component |
| SynGO term: | presynaptic cytosol (GO:0099523) |
| Annotated paper: | Frick P, et al. "Novel antibodies reveal presynaptic localization of C9orf72 protein and reduced protein levels in C9orf72 mutation carriers" Acta Neuropathol Commun. 2018 Aug 3;6(1):72 PMID:30075745 |
| Figure(s): | Figure 1, 2, 4, 5 |
| Annotation description: | Figure 1: antibody characterization Figure 2e,f,g: biochemical fractionation of mouse brain shows that both C9orf72 antibodies are enriched in synaptosomal fractions, and released into the LS2 fraction containing the soluble cytoplasmic content of synaptosomes. Not detected in PSD fraction, suggesting presynaptic localization. Figure 4a: "C9orf72 positive puncta (green) are seen in the axons of 30 day old human iPSC derived motor neurons which consistently co-localize with SMCR8 (red, upper panel) and partially co-localize with LAMP2 as lysosomal marker (red, middle panel) or with the synaptic vesicle marker synaptophysin (red, lower panel). Nuclei are stained with DAPI (blue) in the merged images. C9orf72 labeled with 12E7 antibody in the upper panel and with 1C1 in the middle and lower panel." Figure 4b: Percentage of C9orf72 positive puncta co-localizing with SMCR8 was ~90%, LAMP2 ~41% (lysosomal marker) or synaptophysin ~11% (presynaptic marker). As for the co-staining with SMCR8, authors noted; "Several recent studies have demonstrated that C9orf72 interacts with the SMCR8 protein and regulates the endo-lysosomal and autophagy pathways [1, 21, 45, 48, 51, 54, 57]." Figure 5: C9orf72 complex interacts with members of the RAB3 protein family. Double-label immunofluorescence of 30 day old human iPSC-derived motor neurons showed co-localization of C9orf72 with RAB39B (~22%) or RAB3 (~8%) in a subset of C9orf72-positive puncta. |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | Antibody (detection) |
| Evidence tracking, Experiment Assay: | Western blot Biochemical fractionation (generic) 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: | 4807 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |