ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Cleavage of the vesicular GABA transporter under excitotoxic conditions is followed by accumulation of the truncated transporter in nonsynaptic sites.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 49 citations in OpenAlex.
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- High-resolution micro-CT for 3D infarct characterization and segmentation in mice stroke models.Scientific reports · 2022Article
- Bridging the Transient Intraluminal Stroke Preclinical Model to Clinical Practice: From Improved Surgical Procedures to a Workflow of Functional Tests.Frontiers in neurology · 2022Article
- Transient incubation of cultured hippocampal neurons in the absence of magnesium induces rhythmic and synchronized epileptiform-like activity.Scientific reports · 2021Article
- Phosphorylation of Serine 157 Protects the Rat Glycine Transporter GlyT2 from Calpain Cleavage.Journal of molecular neuroscience : MN · 2020Article
- Neuronal megalin mediates synaptic plasticity-a novel mechanism underlying intellectual disabilities in megalin gene pathologies.Brain communications · 2020Article
- Calpain-dependent cleavage of GABAergic proteins during epileptogenesis.Epilepsy research · 2019Article
- The Roles of GABA in Ischemia-Reperfusion Injury in the Central Nervous System and Peripheral Organs.Oxidative medicine and cellular longevity · 2019Review
- Delivery of an anti-transthyretin Nanobody to the brain through intranasal administration reveals transthyretin expression and secretion by motor neurons.Journal of neurochemistry · 2018Article
- Therapeutic effect of transmembrane TAT-tCNTF via Erk and Akt activation usingInternational journal of clinical and experimental pathology · 2018Article
- Inhibition of Calpains Protects Mn-Induced Neurotransmitter release disorders in Synaptosomes from Mice: Involvement of SNARE Complex and Synaptic Vesicle Fusion.Scientific reports · 2017Article
- Downregulation of GABAMolecular neurobiology · 2017Article
- Transthyretin provides trophic support via megalin by promoting neurite outgrowth and neuroprotection in cerebral ischemia.Cell death and differentiation · 2016Article
- Gephyrin Cleavage in In Vitro Brain Ischemia Decreases GABAA Receptor Clustering and Contributes to Neuronal Death.Molecular neurobiology · 2016Article
- Insulin neuroprotection and the mechanisms.Chinese medical journal · 2015Review
- Transthyretin Induces Insulin-like Growth Factor I Nuclear Translocation Regulating Its Levels in the Hippocampus.Molecular neurobiology · 2015Article
- Optogenetic investigation of the role of the superior colliculus in orienting movements.Behavioural brain research · 2013Article
- Are vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?Frontiers in cellular neuroscience · 2013Review
- Sorting of the vesicular GABA transporter to functional vesicle pools by an atypical dileucine-like motif.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Activity-dependent cleavage of the K-Cl cotransporter KCC2 mediated by calcium-activated protease calpain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GABA is the major inhibitory neurotransmitter in the CNS and changes in GABAergic neurotransmission affect the overall activity of neuronal networks. The uptake of GABA into synaptic vesicles is mediated by the vesicular GABA transporter (VGAT), and changes in the expression of the transporter directly regulate neurotransmitter release. In this work we investigated the changes in VGAT protein levels during ischemia and in excitotoxic conditions, which may affect the demise process. We found that VGAT is cleaved by calpains following excitotoxic stimulation of hippocampal neurons with glutamate, giving rise to a stable truncated cleavage product (tVGAT). VGAT cleavage was also observed after transient middle cerebral artery occlusion in mice, a cerebral ischemia model, and following intrahippocampal injection of kainate, but no effect was observed in transgenic mice overexpressing calpastatin, a calpain inhibitor. Incubation of isolated cerebrocortical synaptic vesicles with recombinant calpain also induced the cleavage of VGAT and formation of stable tVGAT. Immunoblot experiments using antibodies targeting different regions of VGAT and N-terminal sequencing analysis showed that calpain cleaves the transporter in the N-terminal region, at amino acids 52 and 60. Immunocytochemistry of GABAergic striatal neurons expressing GFP fusion proteins with the full-length VGAT or tVGAT showed that cleavage of the transporter induces a loss of synaptic delivery, leading to a homogeneous distribution of the protein along neurites. Our results show that excitotoxicity downregulates full-length VGAT, with a concomitant generation of tVGAT, which is likely to affect GABAergic neurotransmission and may influence cell death during ischemia.
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