| Annotated protein: | Neuritin (Candidate plasticity gene 15 protein). Gene symbol: NRN1. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q8CFV4 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ NRN1 |
| Ontology domain: | Biological Process |
| SynGO term: | presynaptic modulation of chemical synaptic transmission (GO:0099171) |
| Synapse type(s): | cerebral cortex, glutamatergic |
| Annotated paper: | Lu JM, et al. "Neuritin Enhances Synaptic Transmission in Medial Prefrontal Cortex in Mice by Increasing CaV3.3 Surface Expression" Cereb Cortex. 2017 Jul 1;27(7):3842-3855 PMID:28475719 |
| Figure(s): | Figures 1-9 |
| Annotation description: | Neuritin is a small extracellular protein anchored to the cell surface via a glycosyl-phosphoinositide anchor (GPI). Fig. 1: Neuritin significantly increased the frequency of mEPSCs in a concentration- and time-dependent manner." Incubation of mPFC slices with neuritin increased the mEPSC frequency in pyramidal neurons in mPFC layers II/III from cortical slices. No significant effect on mEPSC amplitude was observed. Glutamate concentrations in the ACSF assayed by HPLC, were elevated by neuritin. Fig. 2-3: "Neuritin Increased mEPSC Frequency and Glutamate Release in Pyramidal Neurons Through Activation of IR-Mediated ERK1/2 Pathway." Inhibition of the insulin receptor (IR) with HNMPA (Fig. 2A-B) or MERK/ERK signaling (U0126, Fig. 3B-C) attenuated the effect of neuritin on mEPSC frequency and glutamate release, where as insulin mimicked the effects of neuritin (Fig. 2C-D). Western blot analysis of mPFC slices showed neuritin increased p-ERK1 and p-ERK2 levels (Fig. 3A). Fig. 4-5: "Neuritin Increased Synaptic Transmission in Pyramidal Neurons in the mPFC via T-Type Calcium Channels" Treatment of mPFC slices with the T-type VGCC blockers (NiCl2, 100 μM or mibefradil, 10 μM) reduced the effects of neuritin. Nifedipine (L-type VGCCs) had no effect on the action of neuritin. T-type VGCC current (IT-type VGCC) was significantly increased in pyramidal neurons following neuritin treatment (Fig. 5B). Neuritin-induced potentiation was blocked by IR- or MEK/ERK inhibition. "Neuritin Increased T-Type VGCC Activity by Promoting CaV3.3 Surface Expression" neuritin selectively increased the synaptic membrane expression of CaV3.3 (Fig. 6B-C). This effect was block upon inhibition of the IR or MEK/ERK signaling. Treatment with brefeldin A showed neuritin increased glutamate release by promoting T-type VGCC trafficking to the membrane (Fig. 8). Fig. 9: "AAV9-Mediated Neuritin Knockdown Reduces Synaptic Transmission in mPFC Pyramidal Neurons" Knockdown of neuritin decreased mEPSC frequency and reduced IT-type VGCC amplitudes compared to control neurons. "These results indicate that neuritin is necessary for maintaining synaptic transmission under physiological conditions and that a Ca2+-dependent mechanism is involved." |
| Evidence tracking, Biological System: | Intact tissue Cultured neurons |
| Evidence tracking, Protein Targeting: | RNAi / shRNA Antagonist / agonist Antibody (detection) |
| Evidence tracking, Experiment Assay: | Confocal Whole-cell patch clamp Western blot Biochemical fractionation (generic) |
| Annotator(s): | Hana Goldschmidt (ORCID:0000-0002-5676-366X) Richard Huganir (ORCID:0000-0001-9783-5183) |
| Lab: | Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA and Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD 21205, USA |
| Additional literature: | PMID:9743502 PMID:8515813 |
| SynGO annotation ID: | 2722 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |