| Annotated protein: | Phosphatidylinositol-3-phosphatase SAC1 (EC 3.1.3.64) (Phosphatidylinositol-4-phosphate phosphatase) (Suppressor of actin mutations 1-like protein). Gene symbol: SACM1L. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q9EP69 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ SACM1L |
| Ontology domain: | Biological Process |
| SynGO term: | exocytic insertion of neurotransmitter receptor to postsynaptic membrane (GO:0098967) |
| Synapse type(s): | cerebral cortex, glutamatergic |
| Annotated paper: | Casas M, et al. "Sensing of nutrients by CPT1C controls SAC1 activity to regulate AMPA receptor trafficking" J Cell Biol. 2020 Oct 5;219(10):e201912045 PMID:32931550 |
| Figure(s): | Fig. 6 e and f |
| Annotation description: | Fig. 6 (C) SAC1 silencing increased GluA1 surface levels and abolished the effect of TOFA treatment. Surface GluA1 after TOFA treatment (20 μg/ml, 2 h) was detected in nonpermeabilized neurons by immunocytochemistry. Results are the mean ± SEM from two independent experiments performed by biological duplicates (twoway ANOVA followed by Bonferroni's comparison test; *, P < 0.05 and **, P < 0.01). shRandom + vehicle (1.00 ± 0.09, n = 35), shRandom + TOFA (0.44 ± 0.06, n = 32), shSAC1 + vehicle (0.90 ± 0.13, n = 34), and shSAC1 + TOFA (1.48 ± 0.09, n = 20). Scale bars = 5 μm. n.s, not significant. (F) SAC1 overexpression decreased surface levels of GluA1 and abolished the effect of TOFA treatment in cortical neurons. Neurons, transduced as explained above, were treated with TOFA at 14-15 DIV. Results are the mean ± SEM from two independent experiments performed by biological duplicates (two-way ANOVA followed by Bonferroni's comparison test; ***, P < 0.001). EV + vehicle (1.00 ± 0.05, n = 36), shRandom + TOFA (0.27 ± 0.03, n = 36), SAC1 + vehicle (0.46 ± 0.04, n = 39), and shSAC1 + TOFA (0.36 ± 0.05, n = 36). Scale bars = 5 μm. 16/02/2021 Dnyanada: The paper presents the CPT1C-Malonyl CoA-SAC1 pathway that regulates GluA1 trafficking (Figure 10). SAC1 activity negatively regulates the exocytic insertion of GluA1. CPT1C-Malonyl CoA inhibits SAC1 activity and promotes insertion of GluA1 from the TGN to the plasma membrane. TOFA is an acetyl-CoA analogue that inhibits the malonyl-CoA formation and significantly reduces the levels of GluA1 at the PM compared with control cells. However, treatment with TOFA did not alter the effect of SAC1 on surface GluA1 levels (overexpression led to a decrease and silencing led to an increase) indicating that SAC1 is downstream of the malonyl-CoA/CPT1C axis and directly regulates exocytic insertion of GluA1. |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | RNAi / shRNA Over-expression |
| Evidence tracking, Experiment Assay: | Confocal |
| Annotator(s): | Chiara Verpelli (ORCID:0000-0003-2949-9725) Carlo Sala (ORCID:0000-0003-0662-9523) |
| Lab: | CNR Neuroscience Institute Milan and Dept. of Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy |
| SynGO annotation ID: | 4527 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |