| Annotated protein: | Signal-induced proliferation-associated 1-like protein 1 (SIPA1-like protein 1) (SPA-1-like protein p1294) (Spine-associated Rap GTPase-activating protein) (SPAR). Gene symbol: SIPA1L1. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: O35412 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ SIPA1L1 |
| Ontology domain: | Biological Process |
| SynGO term: | postsynaptic actin cytoskeleton organization (GO:0098974) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Pak DT, et al. "Regulation of dendritic spine morphology by SPAR, a PSD-95-associated RapGAP" Neuron. 2001 Aug 2;31(2):289-303 PMID:11502259 |
| Figure(s): | Fig.3, 4, Fig 7 and Fig. 8 |
| Annotation description: | Fig. 5E-G and Fig 7. Overexpression of SIPA1L1/SPAR promotes the growth of postsynaptic compartment and enlargement of dendritic spines. Literal: "Using GFP expressed from a separate cotransfected plasmid to outline dendrites and spines, we measured the length of spines from the base of the neck to the furthest point on the spine head, and the maximal width of the spine head perpendicular to the long axis of the spine neck (see Figures 7D and 7H) . The mean width of spine heads increased in SPAR neurons (0.86 ± 0.09 μm for SPAR neurons, versus 0.67 ± 0.09 μm for GFP neurons, p < 0.001). The maximum observed spine head width increased ~50%, from 1.5 μm in GFP control neurons to 2.3 μm in SPAR neurons. Due to limitations of the "GFP fill" approach and confocal microscopy, our measurements are not necessarily accurate in an absolute quantitative sense, but are valid for comparing relative dimensions between groups of neurons. A frequency distribution plot of spine head widths revealed that a substantial proportion of spines in SPAR neurons were similar to control (peak between 0.4 and 0.6 μm) (Figure 7J); however, SPAR overexpression induced an additional major peak at 0.8-1.0 μm (Figure 7J; see also cumulative distribution, Figure 7K). A comparison of representative spines at the 95th, 50th, 5th, and 1st percentiles (in order of increasing head size) illustrates the more pronounced difference between SPAR spines and control spines at the upper end of the distribution (Figures 7A-7H). SPAR had no significant effect on the mean length of spines (Figure 7L; 1.41 ± 0.12 μm for SPAR, versus 1.49 ± 0.23 μm for GFP, p = 0.40). Nevertheless, the spines with the largest heads in SPAR transfected neurons were often longer than average, but this effect could be attributed to the increase in head diameter." "The enlarged spine heads in SPAR neurons appeared to be postsynaptic compartments in the sense that they contained PSD-95 (Figure 5E) and were apposed to the presynaptic marker synaptophysin (Figure 5F). Indeed, the SPAR-enlarged spines showed more intense staining for PSD-95 (Figure 5E2, arrow) compared to spines of untransfected cells (Figure 5E2, arrowhead). Moreover, not only did the enlarged spines contact synaptophysin clusters (Figure 5F), the majority (64%) of spines of >1 μm width were apposed to more than one synaptophysin cluster (Figure 5F3, arrows, and data not shown). We found an approximately linear correlation between spine width and number of associated synaptophysin puncta in SPAR-transfected neurons (Figure 7I). In control GFP neurons, less than 2% of spines were apposed to more than a single synaptophysin punctum; these spines were at the upper end of the size distribution for GFP neurons (Figure 7I). These observations suggest that, along with spine head enlargement, SPAR promotes the growth of postsynaptic specializations and possibly the formation of multiple synapses on individual dendritic spines." Fig. 8, overexpression of SIPA1L1/SPAR Effect of SPAR strongly modify dendritic spine shape in cultured hippocampal neurons. Literal: "In SPAR-transfected neurons, however, a substantial proportion of spines, particularly larger spines, were highly irregular in shape (compare Figure 8A with Figure 8F; quantified in Figure 8N). The irregularity of spine shape in SPAR neurons was of two major types: "thorny" spines with sharp projections or outgrowths (Figures 8G-8I), and "multilobed" spines which appeared to have multiple "heads" fused together atop a single neck (Figures 8J-8L). We also measured the maximal crosssectional area of spines by tracing the outlines of the heads using z-series stacks of confocal images, which confirmed that the SPAR neurons possessed larger spines than GFP neurons in terms of spine head area (Figure 8O). The degree of irregularity of spine heads was quantified by the circularity index: the lower the index, the more complex the shape, with a maximal value of 1 for a perfect circle (see Experimental Procedures, and Amaral and Dent, 1981). Plotting area against the circularity index confirmed that spines from SPAR neurons were more complex than those from GFP neurons and established that irregularity was correlated with increased spine head area (Figure 8O). The percentage of branched spines (spines that have two heads and two necks that merge into a single neck at the base; e.g., Figures 8E and 8F) was similar in SPAR and GFP neurons (Figure 8N). Furthermore, SPAR neurons developed slightly fewer spines than control (Figure 8P), making it unlikely that SPAR promotes spine formation." 7/11/2017 Pim - Fig.3: SPAR Reorganizes F-Actin in Heterologous Cells - Fig.4: SPAR Recruits PSD-95 to F-Actin |
| Evidence tracking, Biological System: | Cultured neurons Non-neuronal tissue |
| Evidence tracking, Protein Targeting: | 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: | 1815 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |