ArticleGlia2014
Sumoylation of the astroglial glutamate transporter EAAT2 governs its intracellular compartmentalization.
Article in Glia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- Downregulation of Hmox1 and Rpgrip1l Expression Linked to Risk-Taking Behavior, Reduced Depressive Symptoms, and Diminished Novelty Socialization in SUMO1 Knockout Mice.Cellular and molecular neurobiology · 2025Article
- Topotecan and Ginkgolic Acid Inhibit the Expression and Transport Activity of Human Organic Anion Transporter 3 by Suppressing SUMOylation of the Transporter.Pharmaceutics · 2024Article
- Article
- Astrocytic histone deacetylase 2 facilitates delayed depression and memory impairment after subarachnoid hemorrhage by negatively regulating glutamate transporter-1.Annals of translational medicine · 2020Article
- Exciting Complexity: The Role of Motor Circuit Elements in ALS Pathophysiology.Frontiers in neuroscience · 2020Review
- Transcriptomics and Metabolomics in Amyotrophic Lateral Sclerosis.Advances in experimental medicine and biology · 2020Review
- The role of astrocytic glutamate transporters GLT-1 and GLAST in neurological disorders: Potential targets for neurotherapeutics.Neuropharmacology · 2019Review
- Evidence of adaptation of maternofetal transport of glutamine relative to placental size in normal mice, and in those with fetal growth restriction.The Journal of physiology · 2019Article
- Cellular Proteostasis in Neurodegeneration.Molecular neurobiology · 2019Review
- Post-translational Regulation of GLT-1 in Neurological Diseases and Its Potential as an Effective Therapeutic Target.Frontiers in molecular neuroscience · 2019Review
- Epigenetic Regulation of Excitatory Amino Acid Transporter 2 in Neurological Disorders.Frontiers in pharmacology · 2019Review
- Chronic Unexpected Mild Stress Destroys Synaptic Plasticity of Neurons through a Glutamate Transporter, GLT-1, of Astrocytes in the Ischemic Stroke Rat.Neural plasticity · 2019Article
- Post-translational modifications of transporters.Pharmacology & therapeutics · 2018Review
- Kv1.3 activity perturbs the homeostatic properties of astrocytes in glioma.Scientific reports · 2018Article
- Article
- Regulation of glutamate transporter 1 (GLT-1) gene expression by cocaine self-administration and withdrawal.Neuropharmacology · 2018Article
- Brain endothelial cells induce astrocytic expression of the glutamate transporter GLT-1 by a Notch-dependent mechanism.Journal of neurochemistry · 2017Article
- Glutamate Transport: A New Bench to Bedside Mechanism for Treating Drug Abuse.The international journal of neuropsychopharmacology · 2017Review
- Mutation of the caspase-3 cleavage site in the astroglial glutamate transporter EAAT2 delays disease progression and extends lifespan in the SOD1-G93A mouse model of ALS.Experimental neurology · 2017Article
- Decreased Motor Neuron Support by SMA Astrocytes due to Diminished MCP1 Secretion.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
EAAT2 is a predominantly astroglial glutamate transporter responsible for the majority of synaptic glutamate clearance in the mammalian central nervous system (CNS). Its dysfunction has been linked with many neurological disorders, including amyotrophic lateral sclerosis (ALS). Decreases in EAAT2 expression and function have been implicated in causing motor neuron excitotoxic death in ALS. Nevertheless, increasing EAAT2 expression does not significantly improve ALS phenotype in mouse models or in clinical trials. In the SOD1-G93A mouse model of inherited ALS, the cytosolic carboxy-terminal domain is cleaved from EAAT2, conjugated to SUMO1, and accumulated in astrocytes where it triggers astrocyte-mediated neurotoxic effects as disease progresses. However, it is not known whether this fragment is sumoylated after cleavage or if full-length EAAT2 is already sumoylated prior to cleavage as part of physiological regulation. In this study, we show that a fraction of full-length EAAT2 is constitutively sumoylated in primary cultures of astrocytes in vitro and in the CNS in vivo. Furthermore, the extent of sumoylation of EAAT2 does not change during the course of ALS in the SOD1-G93A mouse and is not affected by the expression of ALS-causative mutant SOD1 proteins in astrocytes in vitro, indicating that EAAT2 sumoylation is not driven by pathogenic mechanisms. Most interestingly, sumoylated EAAT2 localizes to intracellular compartments, whereas non-sumoylated EAAT2 resides on the plasma membrane. In agreement, promoting desumoylation in primary astrocytes causes increased EAAT2-mediated glutamate uptake. These findings could have implications for optimizing therapeutic approaches aimed at increasing EAAT2 activity in the dysfunctional or diseased CNS.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.