Ask about this productRelated genes to: SLC12A5 antibody
- Gene:
- SLC12A5 NIH gene
- Name:
- solute carrier family 12 member 5
- Previous symbol:
- -
- Synonyms:
- KIAA1176, KCC2
- Chromosome:
- 20q13.12
- Locus Type:
- gene with protein product
- Date approved:
- 2000-11-09
- Date modifiied:
- 2016-02-17
Related products to: SLC12A5 antibody
Related articles to: SLC12A5 antibody
- Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in infants and toddlers, with limited treatment options and persistent neurological sequelae. We developed a multi-pathoanatomic lesion multi-insult (MuLMI) severe TBI model in piglets that replicates age-dependent damage patterns to the cortical ribbon observed in human patients with less injury in postnatal day (PND) 7 “infant” piglets and more extensive tissue damage in PND30 “toddler” piglets. Given that neuronal chloride homeostasis influences excitability, seizure susceptibility, and edema, we examined the developmental and injury-induced regulation of key cation-chloride cotransporters and modulators: NKCC1 (sodium-potassium-2-chloride cotransporter), KCC2 (potassium-chloride cotransporter), and the regulatory kinase SPAK, which are biomarkers of neuronal chloride concentrations. This study is the first to define the spatiotemporal expression and phosphorylation profiles of these proteins in the developing piglet brain. We found a perinatal shift in the ratio of KCC2:NKCC1 across the brain, driven primarily by protein abundance, rather than transcriptional levels. We hypothesized that toddler piglets would exhibit an increase in cortical NKCC1 and SPAK causing hyperexcitability and perhaps explaining their more severe, unilateral cortical damage. Severe TBI induced a transcriptional increase in and , and a decrease in in toddler piglets, but not infant piglets. We further found that infant piglets, not toddler piglets, upregulated SPAK and Tyrosine Receptor Kinase B (TRKB) protein in cortex after TBI, with minimal changes in NKCC1 and KCC2. However, phosphorylated NKCC1 (pNKCC1) was significantly upregulated in surviving cortical neurons after TBI in infant piglets and was unchanged in toddlers, despite more severe injury. These findings suggest that cortical neuronal NKCC1 activation may play a role in post-traumatic excitability or resilience in the immature brain and identify NKCC1 and/or SPAK as a potential therapeutic target. In human tissue, the KCC2:NKCC1 ratio also increased postnatally, and TBI caused region and cell-type specific dysregulation of pNKCC1. Our results establish piglets as a valuable model for investigating age-specific mechanisms of pediatric TBI and for testing targeted interventions, particularly for infant populations where seizure control remains a major clinical challenge. - Source: PubMed
Publication date: 2026/02/24
Hochstetler AlexandraCourtney Ya'elOloko PeaceBaskin BenjaminDing-Su AndrewStinson TawnyAlber ElyssaChung David YMcGuone DeclanHaynes RobinLehtinen Maria KCostine-Bartell Beth - Rett syndrome is an X-linked neurodevelopmental disorder resulting from mutations in the MeCP2 gene, leading to intellectual disability, impaired motor coordination, decreased sociability, and seizures. Central to the underlying pathophysiology are deficits in synaptic inhibition, which are mediated by hyperpolarizing GABA R currents. These events develop postnatally and are dependent upon increased neuronal Cl extrusion mediated by SLC12A5 (KCC2). Therefore, we tested whether its activation modifies the disease phenotypes evident in female MeCP2 mice, using OV350, a direct activator of KCC2. OV350 rapidly induced a sustained reduction in EEG power, accompanied by a decrease in the severity of epileptic discharges. Increased motor coordination, sociability, and spatial memory were also observed. Deficits in KCC2 phosphorylation were also seen in MeCP2 mice, consistent with reductions in its activity that were also ameliorated by OV350. Thus, KCC2 activation may be efficacious in limiting the impact of Rett syndrome and other neurodevelopmental disorders. - Source: PubMed
Publication date: 2026/01/13
Arshad Muhammad NaumanNg Shu Fun JosephineSalar SedaAbiraman KrithikaNishi ToshiyaZhong ZhongSmalley Joshua LDavies Paul AMoss Stephen J - Glioblastoma multiforme (GBM), an aggressive brain tumor with a dismal prognosis, lacks robust prognostic biomarkers. In this study, we aimed to identify novel biomarkers using integrative bioinformatics, radiomics, and experimental validation. Using the GEO, TCGA, and CGGA datasets, we screened 387 differentially expressed genes (DEGs) and identified five hub genes (LOX, VEGFA, SERPINH1, SLC12A5, and VSNL1) linked to poor outcomes. Among these, SLC12A5 exhibited unique downregulation in GBM, in contrast to its upregulation in most other cancers. Functional analyses revealed that SLC12A5 suppressed the JAK-STAT3, E2F, and MYC pathways, whereas single-cell sequencing highlighted its predominant expression in astrocytes and microglia. Western blotting and immunohistochemistry validated that SLC12A5 downregulation correlated with increased brain edema volume (negative correlation, * p < 0.05) and activated MMP9/STAT3 signaling. Radiomics analysis demonstrated that SLC12A5 expression was associated with MRI features predictive of the IDH genotypes, offering non-invasive prognostic insights. Drug sensitivity screening identified six small molecules (PD0325901, ERK-6604, paclitaxel, ribociclib, TAF1, and lapatinib) that targeted SLC12A5-related pathways. Crucially, multivariate Cox regression analysis confirmed that SLC12A5 was an independent prognostic factor (HR p = 0.04). This study established SLC12A5 as a novel biomarker for GBM, uniquely bridging molecular dysregulation, edema pathogenesis, and radiomics with implications for prognosis and targeted therapy. - Source: PubMed
Publication date: 2026/01/24
Zhong RongdeKou ZengweiWang HengLi QianXiao YueLi ZongyangChen WeilinChen FanfanHuang GuodongLiu Yunsheng - Neuronal function requires fine-tuned and coordinated activity of several ion channels and transporters. One member of this ensemble is the KCC2 potassium-chloride cotransporter. Because KCC2 expression is required for GABA-dependent inhibitory synaptic transmission, mutations in the gene encoding KCC2 () have been linked to several diseases that also arise from defects in GABA signaling, including epilepsy, schizophrenia, and autism spectrum disorders. Although characterization of the corresponding mutant proteins is ongoing, KCC2 mutants may reside at the cell surface but lack function, they may remain trapped intracellularly and are thus unable to function at the cell surface, or they may be readily degraded. In this article, we summarize these data and emphasize the importance of protein degradation and protease activity during KCC2 quality control, i.e. the pathway that ensures only properly folded and mature KCC2 can traffic to and function at the cell surface. We also highlight how proteolysis regulates the amount of active KCC2 at the cell surface, i.e. KCC2 quantity control. Finally, because previously unidentified KCC2 mutants are continuously being discovered, we discuss the use of predictive pathogenicity algorithms to provide researchers with information on potential disease outcomes. - Source: PubMed
Publication date: 2025/12/23
Kok MorganAizenman EliasGuerriero Christopher JBrodsky Jeffrey L - Binge drinking during adolescence is associated with a higher risk of developing Alcohol Use Disorders and impaired stress reactivity in adulthood. The hypothalamic-pituitary-adrenal axis matures during adolescence and is under strict GABAergic control. Yet, how early binge drinking alters GABAergic signaling in this region, and whether these changes contribute to later-life disruptions in stress reactivity, remain unknown. - Source: PubMed
Publication date: 2025/12/08
Büyükdemirtaş BilgeBenn MilanKwon Han BinRosen EllieMelón Laverne Camille