| Annotated protein: | Ras-related C3 botulinum toxin substrate 1 (EC 3.6.5.2) (p21-Rac1). Gene symbol: RAC1. Taxonomy: Mus musculus (Mouse). Uniprot ID: P63001 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ RAC1 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of synaptic vesicle endocytosis (GO:1900242) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | O'Neil SD, et al. "Action potential-coupled Rho GTPase signaling drives presynaptic plasticity" Elife. 2021 Jul 16;10:e63756 PMID:34269176 |
| Figure(s): | Figure 4 |
| Annotation description: | Figure 4: Presynaptic Rac1 negatively regulates synaptic vesicle replenishment "Since Rac1 also has important functions during neuronal development, synaptogenesis, and postsynaptic plasticity (Govek et al., 2005; Hedrick and Yasuda, 2017; Tolias et al., 2011), we devised a system to isolate its mature presynaptic function by using a mixed hippocampal culture system where presynaptic wildtype (WT) or knock-out (KO) neurons expressed channelrhodopsin (ChR2), and light-evoked responses were recorded from postsynaptic WT neurons. ... In this system, loss of Rac1 is not expected until after synaptic maturation, assuming ~24 hr for Cre expression to begin and ~72 hr for turnover of the endogenous protein. ... Presynaptic Rac1 deletion did not affect the amplitude, charge transfer, or kinetics of single evoked EPSCs (Figure 4-figure supplement 2A,B,E). It also did not affect the paired pulse ratio (PPR) (Figure 4C). ... Finally, a high-frequency stimulation (HFS) train was used to probe synaptic vesicle recycling. ... Surprisingly, presynaptic Rac1 deletion reduced short-term synaptic depression in response to HFS (Figure 4E). There was no effect on asynchronous release during the train, as measured by the steady-state basal current (Figure 4-figure supplement 2C,F). Quantification of the cumulative EPSC curve showed that presynaptic Rac1 deletion increased the synaptic vesicle replenishment rate, without altering release probability or RRP size. Presynaptic Rac1 deletion from inhibitory neurons caused similar effects as in excitatory neurons; there were no effects on single evoked IPSCs (Figure 4-figure supplement 2G), PPR (Figure 4F), quantal events (Figure 4G), or asynchronous release during HFS trains (Figure 4-figure supplement 2D,H). However, there was a reduction in the short-term depression of IPSCs due to an increase in the synaptic vesicle replenishment rate (Figure 4H). Together, these data show that Rac1 negatively regulates synaptic vesicle replenishment at both excitatory and inhibitory synapses, suggesting that this is a common function of Rac1 across different kinds of presynaptic terminals." |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) |
| Evidence tracking, Experiment Assay: | Whole-cell patch clamp Optical physiology |
| 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: | 5368 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |