| Annotated protein: | Inositol-trisphosphate 3-kinase A (EC 2.7.1.127) (Inositol 1,4,5-trisphosphate 3-kinase A) (IP3 3-kinase A) (IP3K A) (InsP 3-kinase A). Gene symbol: ITPKA. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: P17105 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ ITPKA |
| Ontology domain: | Biological Process |
| SynGO term: | modification of postsynaptic actin cytoskeleton (GO:0098885) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Kim IH, et al. "Inositol 1,4,5-trisphosphate 3-kinase a functions as a scaffold for synaptic Rac signaling" J Neurosci. 2009 Nov 4;29(44):14039-49 PMID:19890013 |
| Figure(s): | Fig.1, 2, 3, 4, 6, 7 |
| Annotation description: | Fig.1: "IP3K-A accumulates in dendritic spines upon LTP induction" Fig.2: "IP3K-A promotes dendritic spine formation" - "Following transfection of IP3K-A-siRNA in combination with GFP-expressing vectors into DIV 22 hippocampal neurons, GFP+ neurons exhibited markedly reduced IP3K-A expression (Figure 2A). Quantification revealed that the density of dendritic spines was also greatly reduced in IP3K-A-siRNA-transfected/GFP+ neurons when compared with control-siRNA-transfected/GFP+ neurons (t=14.17, df=52, p<.0001)." Fig.3: "IP3K-A influences actin dynamics and binds directly to only activated Rac1" Fig.4: "Rac1 activity is essential for IP3K-A to exert its effects on dendritic spines" - "When HeLa cells were treated with a Rac1-specific inhibitor (NSC23766) filopodia formation induced by GFP-IP3K-A was blocked, suggesting that Rac1 activity is essential for IP3K-A's effects on cellular actin (Figure 4A)." Fig.6: "IP3K-A recruits activated Rac1 onto F-actin fibers" - "Furthermore, p-PAK-IRs were dramatically merged with overexpressed GFP-IP3K-A signals, which are localized on the F-actin in the head of dendritic protrusions (Figure 3A and Figure 6C), suggesting that IP3K-A-dependent targeting of activated Rac onto F-actin cytoskeleton also occurs in neurons." Fig.7: "IP3K-A knockout mice show defects in LTP and actin dynamics in dentate gyrus" - "we examined whether adult IP3K-A KO mice have defects in neural activation-induced accumulation of F-actin and PAK1 in the synaptic area of dentate gyrus (DG). Following tetanic stimulation in the perforant path of 3-month-old mice, we observed less PAK1 and F-actin in MML and OML of the DG in KO mice when compared with littermate controls (t=43.81, df=4, p<.0001 for PAK1; t=8.50, df=4, p<.001 for F-actin) (Figures 7A and 7B), suggesting that IP3K-A plays an essential role in activated Rac targeting as well as in activity-dependent actin dynamics in DG neurons in vivo." |
| Evidence tracking, Biological System: | Intact tissue Cultured neurons Non-neuronal tissue |
| Evidence tracking, Protein Targeting: | RNAi / shRNA Over-expression Antibody (detection) |
| Evidence tracking, Experiment Assay: | Confocal Field recordings Western blot IP + WB/MSMS |
| Annotator(s): | Pim van Nierop (ORCID:0000-0003-0593-3443) 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: | 3035 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |