Ask about this productRelated genes to: SLC22A15 antibody
- Gene:
- SLC22A15 NIH gene
- Name:
- solute carrier family 22 member 15
- Previous symbol:
- -
- Synonyms:
- FLIPT1
- Chromosome:
- 1p13.1
- Locus Type:
- gene with protein product
- Date approved:
- 2003-10-08
- Date modifiied:
- 2016-10-05
Related products to: SLC22A15 antibody
Related articles to: SLC22A15 antibody
- Creatine, α-N-methyl-guanidino-acetic acid, plays a fundamental role in the storage and regeneration of high-energy phosphate in the brain. Defects in the creatine transporter gene (CRT/SLC6A8) result in a significant reduction in brain creatine levels and severe neurological symptoms such as intellectual disability. Clarifying creatine dynamics in the brain is essential to increase our understanding of CRT deficiency syndrome (CRTD) pathology and the development of CRTD therapeutics. This review comprehensively summarizes the pathophysiological roles of transporters in dynamics of creatine and related guanidine compounds in the brain barriers and brain parenchyma. Brain creatine dynamics are regulated by the cooperative actions of various influx and efflux transporters of creatine, guanidinoacetate, creatinine, and creatine biosynthetic enzymes. These transporters include CRT/SLC6A8 as a creatine/guanidinoacetate/creatinine influx transporter, MCT12/SLC16A12, and SLC22A15 for creatine efflux transport, TauT/SLC6A6, GAT2/SLC6A13, and GAT3/SLC6A11 for guanidinoacetate influx transport, and OCT3/SLC22A3 for creatinine influx transport. Transporters and creatine biosynthetic enzymes, such as arginine-glycine amidinotransferase and guanidinoacetate N-methyltransferase, exhibit cell-type specific spatio-temporal expression at the brain barrier and in neurons, astrocytes, and oligodendrocytes. To date, no effective therapeutics have been developed for the treatment of CRTD. The link between low brain creatine level and the mechanism of neurological dysfunction remains unclear. Creatine prodrugs, molecular chaperones, and adeno-associated virus-based gene therapies are potential therapeutic options for CRTD. Advanced technologies, such as omics and genetic engineering, will open new avenues for CRTD therapeutics. - Source: PubMed
Tachikawa Masanori - Cancers are associated with extensive reorganisation of epigenetic patterns, making identification of DNA methylation changes responsible for driving cancer development challenging. Here, we present a novel approach, integrative methylation mapping, which overcomes this, enabling identification of functionally relevant methylation-regulated genes in cancer. - Source: PubMed
Publication date: 2025/10/31
Lalchungnunga HAtasoy HandeSchwalbe Edward CBacon Chris MStrathdee Gordon - Sepsis remains a leading cause of global morbidity and mortality. - Source: PubMed
Publication date: 2025/04/29
Tao WentingChen Liang - The functional characterization of plasma membrane transport proteins often relies on their heterologous expression in cultured cells. However, some transporters exhibit low activity, hindering meaningful functional assays. Heterologous expression is usually based on strong viral promoters which in living cells are prone to promoter silencing, a major problem. Here, we investigated the efficacy of low-cost histone deacetylase (HDAC) inhibitors in enhancing transporter activity, comparing the established sodium butyrate (the sodium salt of butyric acid) with valproate/valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, also known as vorinostat). Using 293 cells stably transfected with pEBTet plasmids containing the CMV promotor to express the transporters SLC16A9, SLC22A15, and OATP1A2, we measured substrate efflux or uptake via LC-MS/MS following overnight preincubation with the HDAC inhibitors. All three compounds markedly stimulated transporter activity. VPA was less effective than butyrate but still surpassed control conditions. SAHA was cytotoxic at 6 μm, but at 2 μm, the enhancement was consistently comparable to 5 mm butyrate. Additionally, SAHA was more cost-effective and devoid of the repulsive odor characteristic of butyrate. Our findings advocate for replacing butyrate with SAHA to enhance heterologously expressed transporter activity. This offers a more efficient and user-friendly alternative for functional assays. - Source: PubMed
Publication date: 2025/03/07
Flögel SvenjaTust MauriceBoussettaoui SamiraFischer DietmarGründemann Dirk - Creatine is essential for ATP regeneration in energy-demanding cells. Creatine deficiency results in severe neurodevelopmental impairments. In the brain, creatine is synthesized locally by oligodendrocytes to supply neighboring neurons. Neuronal uptake is mediated by SLC6A8. However, it is still unknown how creatine is released from the producing cells. Here, we investigated the function of the transporter SLC22A15, which exhibits strikingly high amino acid sequence conservation. The release of substrates from 293 cells via heterologously expressed human and rat SLC22A15 was analyzed by mass spectrometry. A number of zwitterions were identified as substrates, with similar efflux transport efficiencies. However, in absolute numbers, the efflux of creatine far outweighed all other substrates. In contrast to the permanent creatine efflux mediated by SLC16A12 and SLC16A9, SLC22A15 was, by default, completely inactive, thereby preventing continuous creatine loss from producing cells. External substrates such as guanidinoacetic acid, GABA, or MPP trigger creatine release through a one-to-one exchange. Human and mouse mRNA profiles indicate that SLC22A15 expression is highest in oligodendrocytes and bone marrow. Single-cell RNA sequencing data substantiate the hypothesis that SLC22A15 depends on high intracellular creatine concentrations: high SLC22A15 counts, as in oligodendrocytes and macrophages, correlate with high counts of the creatine synthesis enzymes AGAT and GAMT in both humans and mice, whereas in proximal tubular cells and hepatocytes, AGAT counts are high, but SLC22A15 is absent. Our findings establish SLC22A15 as the pivotal transporter for controlled creatine release from oligodendrocytes, filling a critical gap in understanding creatine metabolism in the brain. - Source: PubMed
Publication date: 2025/01/10
Flögel SvenjaStrater MiriamFischer DietmarGründemann Dirk