Ask about this productRelated genes to: SLC1A2 Blocking Peptide
- Gene:
- SLC1A2 NIH gene
- Name:
- solute carrier family 1 member 2
- Previous symbol:
- -
- Synonyms:
- GLT-1, EAAT2
- Chromosome:
- 11p13
- Locus Type:
- gene with protein product
- Date approved:
- 1994-02-15
- Date modifiied:
- 2016-02-17
Related products to: SLC1A2 Blocking Peptide
Related articles to: SLC1A2 Blocking Peptide
- Glutamate transporters are essential for maintaining CNS homeostasis by clearing extracellular glutamate following synaptic transmission. Dysregulation of these transporters contributes to glutamate-mediated excitotoxicity across numerous neurological disorders, including ischemic stroke, underscoring their potential as therapeutic targets. However, the regulatory response of these transporters following ischemic insult remains poorly defined. In this study, using a model of oxygen-glucose deprivation in primary rat glial cultures, we report aberrant trafficking of the astrocytic glutamate transporter GLT-1 following ischemic insult. This response is characterized by increased transporter internalization and degradation, accompanied by reduced glutamate uptake capacity. Focusing on post-translational modifications (PTMs), we found that GLT-1 ubiquitination is markedly increased after ischemic insult and coincides with transporter internalization. Importantly, disrupting this ubiquitination interaction through mutation of C-terminal GLT-1 lysine residues restores GLT-1 surface expression and rescues glutamate uptake capacity through preventing early endosome 1 (EEA1)-mediated internalization. Additionally, we report that inhibition of C-terminal GLT-1 PTMs confers neuroprotection following ischemic insult in organotypic hippocampal brain slices. Together, these findings demonstrate that ischemia-induced dysregulation of GLT-1 trafficking plays a critical role in impaired glutamate clearance and cellular recovery, highlighting GLT-1 ubiquitination as a potential therapeutic target for ischemic injury. - Source: PubMed
Gill Simran KaurReeb Katelyn LouiseKroll MaxMortensen Ole VFontana Andréia C K - Stroke is one of the most prevalent causes of death and disability worldwide and places a heavy economic burden on families and society. High glutamate accumulation and subsequent excitotoxicity after ischemia and hypoxia are important pathogenetic mechanisms of brain injury after ischemic stroke. Glutamate transporter 1 (GLT-1) on astrocyte membranes is responsible for 90% of glutamate clearance. The involvement of the mTOR/Akt pathway in the upregulation of GLT-1 expression in astrocytes under oxygen-glucose deprivation and reoxygenation conditions has been demonstrated. Nevertheless, it is still unclear whether there is a negative feedback pathway from mTOR to Akt during cerebral ischemia/reperfusion (I/R). It has also not been elucidated whether the mTOR/Akt pathway is involved in the expression of astrocyte GLT-1 in cerebral I/R injury. In this study, we established a middle cerebral artery occlusion-reperfusion rat model to investigate the interactions and mechanisms of the mTOR/Akt cascade with GLT-1 under cerebral I/R conditions. These results provide evidence that brain I/R injury activates the mTOR/Akt pathway in the ischemic penumbra, increases astrocyte activation, and downregulates the expression of GLT-1. Inhibition of the mTOR pathway reversed GLT-1 downregulation and inhibited astrocyte activation by blocking the mTOR pathway, thereby attenuating neurological dysfunction, inflammatory response, and apoptosis caused by brain I/R injury. In contrast, inhibiting the Akt pathway did not provide neuroprotection, with no significant decrease in the number of astrocytes, inflammatory response, or apoptosis in the model group. Additionally, the inhibition downregulated GLT-1 expression and promoted the lengthening and thickening of astrocyte processes in cerebral ischemic rats. Thus, the mTOR/Akt cascade may be involved in regulating astrocyte growth and GLT-1 expression during brain I/R injury. Furthermore, inhibiting the mTOR pathway may mitigate apoptosis and the release of inflammatory factors, thereby fostering neuronal survival and safeguarding the central nervous system. - Source: PubMed
Publication date: 2026/06/12
Li QiulingYu YiwenDeng HuanLi BiaoZhao HaoLei DongLi MiXie ShanshaYu JingmeiZhao YupingYin ShubinJi YiFei - Glutamate spillover from excitatory synapses modulates neighboring inhibitory synapses, yet the ultrastructural organization of the major glutamate transporter GLT-1 at these sites remains poorly defined. Using quantitative pre-embedding electron microscopy in rat and human cortex, we found that GLT-1-positive astrocytic leaflets (ALs) were frequently juxtaposed to morphologically identified symmetric synapses, with similar prevalence across axo-somatic, proximal axo-dendritic, and distal axo-dendritic subtypes. Because inhibitory synapses are embedded in a dense excitatory neuropil, we applied distance-based phenotyping relative to the nearest asymmetric synapse to define symmetric-associated GLT-1+ ALs. Within this population, distal axo-dendritic symmetric synapses showed shorter AL-to-synaptic-edge distances and were embedded in a tighter local excitatory microenvironment. Post-embedding immunogold further showed that GLT-1 was enriched at the plasma membranes of ALs and localized extrasynaptically relative to symmetric synapses. Consistently, symmetric-associated membrane GLT-1 and closely spaced GLT-1/α2 couples (with an interdistance ≤ 50 nm) were preferentially localized within 1000 nm of distal symmetric synapses compared to proximal. Similar organizational features of membrane GLT-1/α2 couples were observed in human cortex. These findings identify a subtype-dependent extrasynaptic astrocytic GLT-1 organization at cortical inhibitory synapses and provide a morphological framework for glutamate-dependent modulation of inhibitory signaling. - Source: PubMed
Melone MarcelloDi Palma MichaelScimemi AnnalisaConti Fiorenzo - Traumatic brain injury (TBI) is a significant health problem around the world. Even mild TBI (mTBI) can cause long-term neurodegenerative consequences such as Alzheimer's disease. Excitotoxicity plays a vital role in neuronal death after TBI, and Glutamate Transporter 1 (GLT-1) may be a therapeutic target for reducing TBI outcomes. It has been found that ceftriaxone (a beta-lactam antibiotic) can reduce TBI symptoms, including astrocyte reactivity and inflammation, and may also affect GLT-1 expression. The primary objective of this study is to investigate how ceftriaxone affects GLT-1 in neurons and astrocytes. mTBI was modelled in male albino mice using a modified Marmarou's weight-drop method. Ceftriaxone (250 mg/kg) was administered intraperitoneally for 3 and 5 days after injury. We immunolabeled coronal brain slices to detect GLT-1 expression and distribution, using antibodies to Glial Fibrillary Acidic Protein (GFAP - astrocytic marker), NeuN (neuronal marker), and GLT-1. The presence of fluorescently labelled areas and the ratio of fluorophores within each area were examined using an image processing plugin that identifies regions with substantial staining in confocal microscopy images. In this article, we address the dynamics of changes in fluorescence intensity and area for the regions we describe as GFAP, NeuN, and GLT-1. We found that GLT-1 dynamics change in both neurons and astrocytes following mTBI, but ceftriaxone affects these changes. In our opinion, due to the displacement of glutamate transporter clusters in cells, they cannot properly fulfil their function of limiting excitability produced by trauma. - Source: PubMed
Publication date: 2026/05/08
Naumenko YanaOlifirov BorysYuryshynets IradaPivneva Tetyana - Recurrent miscarriage (RM), a complex pregnancy disorder with largely undefined molecular mechanisms, has been associated with epigenetic abnormalities in chorionic tissue. This study aimed to elucidate methylation-dependent cilia-related genes (CRGs) implicated in RM. An integrative analysis combining RNA sequencing, public transcriptome data, and DNA methylation profiles was conducted to identify RM-related CRGs. Machine learning algorithms were applied to determine the most relevant candidates. Immune infiltration profiling, gene set enrichment analysis (GSEA), and competitive endogenous RNA (ceRNA) network construction were employed to clarify molecular pathways. RT-qPCR validation was performed using clinical samples. Fourteen methylation-regulated CRGs were identified, among which SLC1A2 and ZDHHC20 were confirmed as key candidates. GSEA indicated their association with spliceosome, cell cycle, and proteasome pathways. Immune analysis demonstrated decreased infiltration of activated CD4 T cells, effector memory CD4 T cells, and Th2 cells in RM, with SLC1A2 and ZDHHC20 expression positively correlated with these immune subsets. The ceRNA networks indicated that SLC1A2 and ZDHHC20 were modulated by 7 miRNAs and 19 lncRNAs, respectively. RT-qPCR results showed significant overexpression of SLC1A2, but not ZDHHC20, in RM chorionic tissue. Collectively, SLC1A2 represents a methylation-regulated CRG that links ciliary impairment, immune imbalance, and epigenetic modulation in RM, revealing a novel molecular axis and suggesting its diagnostic and therapeutic potential. - Source: PubMed
Publication date: 2026/05/09
Li JingJing JunningLiu JingtingZhang DengcaiZhang LiyuanXie Guangmei