| Annotated protein: | H(+)/Cl(-) exchange transporter 3 (Chloride channel protein 3) (ClC-3) (Chloride transporter ClC-3). Gene symbol: CLCN3. Taxonomy: Mus musculus (Mouse). Uniprot ID: P51791-1 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ CLCN3 |
| Ontology domain: | Biological Process |
| SynGO term: | synaptic vesicle proton loading (GO:0097401) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Stobrawa SM, et al. "Disruption of ClC-3, a chloride channel expressed on synaptic vesicles, leads to a loss of the hippocampus" Neuron. 2001 Jan;29(1):185-96 PMID:11182090 |
| Figure(s): | Fig. 8 B and C, Fig. 9 |
| Annotation description: | By acidification (Fig 8 B) and glutamate uptake assays (Fig. 8 C), Stobrawa et al. show that SVs (LP2 fraction) from ClC-3 KO mice acidify at slower rates and that the glutamate uptake by the SVs is significantly reduced. This data suggests that ClC-3 mediates the Cl- conductance in the majority of the SVs. In addition VGLUT1 expression in the KO SVs is also reduced together with attenuated glutamate uptake activity of the vesicles (fig. 8C). Thus, the finding of reduced Cl- conductance in KO mice, considering the reports of other groups, can be alternatively explained by the reduction of VGLUT1 expression rather than the loss of ClC-3. Overall, additional experimental evidence for the Cl- conductance by ClC-3 is required. |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) |
| Evidence tracking, Experiment Assay: | Whole-cell patch clamp Biochemical fractionation (generic) Transmembrane transport assay |
| Annotator(s): | Momchil Ninov (ORCID:0000-0002-0808-7003) Mahdokht Kohansalnodehi (ORCID:0000-0002-3898-5197) Reinhard Jahn (ORCID:0000-0003-1542-3498) |
| Lab: | Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany |
| Additional literature: | The authors of the study use combination of electrophisiology (to track changes in synaptic transmission (mIPSC) in ClC-3 KO mice) and immunoisolation/depletion to show the relevance of ClC-3 for acidification of VGAT-positive synaptic vesicles. @ PMID:21378974 the Authors demonstrate that overexpression of VGLUT1 in PC12 cells can lead to Cl- induced AO quenching (same method to test ATP-induced Cl-dependent acidification of SVs as in the primary paper). @ PMID:10938000 The authors find that VGLUT1 conducts the permeation of Cl- into synaptic vesicles. Furthermore, by using reconstituted VGLUT1, Schenck et al show that glutamate transport is dependent on extracellular Cl-, which is permeates the membrane through the transporter. In addition, a reduction in Cl- induced acidification is not observed for SVs prepared from young ClC-3 KO mice. @ PMID:19169251 |
| SynGO annotation ID: | 377 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |