Slc7a11

Summary

Gene Symbol: Slc7a11
Description: solute carrier family 7 (cationic amino acid transporter, y+ system), member 11
Alias: 9930009M05Rik, AI451155, sut, xCT, cystine/glutamate transporter, amino acid transport system xc-, cysteine/glutamate transporter, sodium independent anionic amino acid transport system, solute carrier family 7 member 11
Species: mouse
Products:     Slc7a11

Top Publications

  1. Mandal P, Seiler A, Perisic T, Kölle P, Banjac Canak A, Forster H, et al. System x(c)- and thioredoxin reductase 1 cooperatively rescue glutathione deficiency. J Biol Chem. 2010;285:22244-53 pubmed publisher
    ..Using three genetically defined cellular systems, we show here that forced expression of xCT, the substrate-specific subunit of the cystine/glutamate antiporter, in gamma-glutamylcysteine synthetase knock-out ..
  2. Iuchi Y, Kibe N, Tsunoda S, Okada F, Bannai S, Sato H, et al. Deficiency of the cystine-transporter gene, xCT, does not exacerbate the deleterious phenotypic consequences of SOD1 knockout in mice. Mol Cell Biochem. 2008;319:125-32 pubmed publisher
    ..The cystine/glutamate transporter, which consists of two proteins, xCT and 4F2hc, has been designated system x (c) (-) ...
  3. Sasaki H, Sato H, Kuriyama Matsumura K, Sato K, Maebara K, Wang H, et al. Electrophile response element-mediated induction of the cystine/glutamate exchange transporter gene expression. J Biol Chem. 2002;277:44765-71 pubmed
    ..System x(c)- consists of two protein components, xCT and the heavy chain of 4F2 antigen...
  4. Massie A, Schallier A, Kim S, Fernando R, Kobayashi S, Beck H, et al. Dopaminergic neurons of system x(c)?-deficient mice are highly protected against 6-hydroxydopamine-induced toxicity. FASEB J. 2011;25:1359-69 pubmed publisher
    ..We used mice lacking xCT (xCT(-/-) mice), the specific subunit of system x(c)(-), to investigate the involvement of this antiporter in PD...
  5. Sato H, Nomura S, Maebara K, Sato K, Tamba M, Bannai S. Transcriptional control of cystine/glutamate transporter gene by amino acid deprivation. Biochem Biophys Res Commun. 2004;325:109-16 pubmed
    ..This transporter is composed of two protein components, xCT and 4F2 heavy chain, and xCT is thought to mediate the transport activity...
  6. Qiao H, Hao C, Li Y, He X, Chen R, Cui J, et al. JNK activation mediates the apoptosis of xCT-deficient cells. Biochem Biophys Res Commun. 2008;370:584-8 pubmed publisher
    ..The underlying mechanism of cell death of cultured cells from the subtle gray (sut) mouse which contains an xCT null mutation remains elucidated...
  7. Shih A, Erb H, Sun X, Toda S, Kalivas P, Murphy T. Cystine/glutamate exchange modulates glutathione supply for neuroprotection from oxidative stress and cell proliferation. J Neurosci. 2006;26:10514-23 pubmed
    ..Conversely, astrocytes and meningeal cells derived from sut/sut mice (xCT loss-of-function mutants) showed greatly reduced proliferation in culture attributable to increased ..
  8. De Bundel D, Schallier A, Loyens E, Fernando R, Miyashita H, Van Liefferinge J, et al. Loss of system x(c)- does not induce oxidative stress but decreases extracellular glutamate in hippocampus and influences spatial working memory and limbic seizure susceptibility. J Neurosci. 2011;31:5792-803 pubmed publisher
    ..We report that mice lacking the specific xCT subunit of system x(c)- (xCT(-/-)) do not have a lower hippocampal glutathione content, increased oxidative stress ..
  9. Sato H, Tamba M, Ishii T, Bannai S. Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins. J Biol Chem. 1999;274:11455-8 pubmed
    ..The latter protein, named xCT, showed a significant homology with those recently reported to mediate cationic or zwitterionic amino acid ..

More Information

Publications60

  1. Chen R, Song Y, Zhou Z, Tong T, Li Y, Fu M, et al. Disruption of xCT inhibits cancer cell metastasis via the caveolin-1/beta-catenin pathway. Oncogene. 2009;28:599-609 pubmed publisher
    b>xCT, the functional subunit of the cystine/glutamate transporter xc- system, plays a critical role in the maintenance of intracellular glutathione and redox balance...
  2. Chintala S, Li W, Lamoreux M, Ito S, Wakamatsu K, Sviderskaya E, et al. Slc7a11 gene controls production of pheomelanin pigment and proliferation of cultured cells. Proc Natl Acad Sci U S A. 2005;102:10964-9 pubmed
    ..Here, we demonstrate that the subtle gray (sut) mouse pigmentation mutant arose by means of a mutation in the Slc7a11 gene, encoding the plasma membrane cystine/glutamate exchanger xCT [Kanai, Y. & Endou, H. (2001) Curr...
  3. Burdo J, Dargusch R, Schubert D. Distribution of the cystine/glutamate antiporter system xc- in the brain, kidney, and duodenum. J Histochem Cytochem. 2006;54:549-57 pubmed
    ..of the main transporters responsible for central nervous system cystine transport, is comprised of two subunits, xCT and 4F2hc...
  4. Qin S, Colin C, Hinners I, Gervais A, Cheret C, Mallat M. System Xc- and apolipoprotein E expressed by microglia have opposite effects on the neurotoxicity of amyloid-beta peptide 1-40. J Neurosci. 2006;26:3345-56 pubmed
    ..This may be relevant to Abeta toxicity in AD, because the system Xc(-)-specific xCT gene is expressed not only in cultured microglia but also in reactive microglia within or surrounding amyloid ..
  5. Soria F, Zabala A, Pampliega O, Palomino A, Miguelez C, Ugedo L, et al. Cystine/glutamate antiporter blockage induces myelin degeneration. Glia. 2016;64:1381-95 pubmed publisher
    ..Here, we analyzed expression of the catalytic subunit of the cystine/glutamate antiporter, xCT, by immunohistochemistry in histological sections of the forebrain and spinal cord...
  6. Albrecht P, Lewerenz J, Dittmer S, Noack R, Maher P, Methner A. Mechanisms of oxidative glutamate toxicity: the glutamate/cystine antiporter system xc- as a neuroprotective drug target. CNS Neurol Disord Drug Targets. 2010;9:373-82 pubmed
    ..It is composed of a specific light chain, xCT, and a heavy chain, 4F2, linked by a disulfide bridge...
  7. Sato H, Shiiya A, Kimata M, Maebara K, Tamba M, Sakakura Y, et al. Redox imbalance in cystine/glutamate transporter-deficient mice. J Biol Chem. 2005;280:37423-9 pubmed
    ..This transporter consists of two protein components, xCT and 4F2 heavy chain, and the former is predicted to mediate the transport activity...
  8. Lin X, Yang H, Zhang H, Zhou L, Guo Z. A novel transcription mechanism activated by ethanol: induction of Slc7a11 gene expression via inhibition of the DNA-binding activity of transcriptional repressor octamer-binding transcription factor 1 (OCT-1). J Biol Chem. 2013;288:14815-23 pubmed publisher
    Solute carrier family 7, member 11 (Slc7a11) is a plasma membrane cystine/glutamate exchanger that provides intracellular cystine to produce glutathione, a major cellular antioxidant...
  9. Uno K, Takarada T, Nakamura Y, Fujita H, Hinoi E, Yoneda Y. A negative correlation between expression profiles of runt-related transcription factor-2 and cystine/glutamate antiporter xCT subunit in ovariectomized mouse bone. J Pharmacol Sci. 2011;115:309-19 pubmed
    ..In this study, we investigated the expression profile of the xCT subunit of the antiporter as well as the master regulator of osteoblastogenesis runt-related transcription factor-2 ..
  10. McCullagh E, Featherstone D. Behavioral characterization of system xc- mutant mice. Behav Brain Res. 2014;265:1-11 pubmed publisher
    The slc7a11 gene encodes xCT, an essential component of 'system xc-', a plasma membrane exchanger that imports cystine and exports glutamate. Slc7a11 is expressed primarily in the brain, but its role there is not clear...
  11. Soria F, Perez Samartin A, Martin A, Gona K, Llop J, Szczupak B, et al. Extrasynaptic glutamate release through cystine/glutamate antiporter contributes to ischemic damage. J Clin Invest. 2014;124:3645-55 pubmed publisher
    ..Altogether, these data suggest that cystine/glutamate antiporter function is increased in ischemia, contributing to elevated extracellular glutamate concentration, overactivation of extrasynaptic NMDARs, and ischemic neuronal death. ..
  12. Campbell A, Bushman J, Munger J, Noble M, Pröschel C, Mayer Pröschel M. Mutation of ataxia-telangiectasia mutated is associated with dysfunctional glutathione homeostasis in cerebellar astroglia. Glia. 2016;64:227-39 pubmed publisher
    ..astroglia isolated from Atm mutant mice show decreased expression of the cystine/glutamate exchanger subunit xCT, glutathione (GSH) reductase, and glutathione-S-transferase...
  13. Zheng X, Li Y, Zhao R, Yan F, Ma Y, Zhao L, et al. xCT deficiency induces autophagy via endoplasmic reticulum stress activated p38-mitogen-activated protein kinase and mTOR in sut melanocytes. Eur J Cell Biol. 2016;95:175-81 pubmed publisher
    xCT, the functional subunit of the system xc(-) encoded by the Slc7a11 gene, plays an important role in maintaining intracellular glutathione (GSH) levels...
  14. Swank R, Reddington M, Novak E. Inherited prolonged bleeding time and platelet storage pool deficiency in the subtle gray (sut) mouse. Lab Anim Sci. 1996;46:56-60 pubmed
    ..The coat color of the subtle gray (sut) mouse is diluted to a relatively minor degree...
  15. Lewerenz J, Maher P. Basal levels of eIF2alpha phosphorylation determine cellular antioxidant status by regulating ATF4 and xCT expression. J Biol Chem. 2009;284:1106-15 pubmed publisher
    ..This correlates with impaired glutathione metabolism because of down-regulation of the light chain, xCT, of the cystine/glutamate antiporter system X(-)(c)...
  16. Nasca C, Bigio B, Zelli D, De Angelis P, Lau T, Okamoto M, et al. Role of the Astroglial Glutamate Exchanger xCT in Ventral Hippocampus in Resilience to Stress. Neuron. 2017;96:402-413.e5 pubmed publisher
    ..regulates glutamate homeostasis in the dorsal and ventral hippocampus and identify a role for the astroglial xCT in ventral dentate gyrus (vDG) in stress and antidepressant responses...
  17. Sakakura Y, Sato H, Shiiya A, Tamba M, Sagara J, Matsuda M, et al. Expression and function of cystine/glutamate transporter in neutrophils. J Leukoc Biol. 2007;81:974-82 pubmed
    ..Cystine/glutamate transporter, designated as system xc- and consisting of two proteins, xCT and 4F2hc, is important to maintain GSH levels in mammalian-cultured cells...
  18. Bentea E, Demuyser T, Van Liefferinge J, Albertini G, Deneyer L, Nys J, et al. Absence of system xc- in mice decreases anxiety and depressive-like behavior without affecting sensorimotor function or spatial vision. Prog Neuropsychopharmacol Biol Psychiatry. 2015;59:49-58 pubmed publisher
    ..As such, modulation of system xc- might constitute the basis of innovative interventions in mood disorders. ..
  19. Sato H, Kuriyama Matsumura K, Hashimoto T, Sasaki H, Wang H, Ishii T, et al. Effect of oxygen on induction of the cystine transporter by bacterial lipopolysaccharide in mouse peritoneal macrophages. J Biol Chem. 2001;276:10407-12 pubmed
    ..System x(c)(-) is composed of two protein components, xCT and 4F2hc, and the expression of xCT was closely correlated with system x(c)(-) activity...
  20. Takaki M, Ueda Y, Doi T, Nagatomo K, Murashima Y, Kannan H. Molecular regulation of antioxidant ability in the hippocampus of EL mice. Brain Res. 2008;1228:1-5 pubmed publisher
    ..concentration, we tried to determine whether or not changes in the expression of cystine/glutamate exchanger (xCT) and glutamate transporter take place in the Hipp of EL...
  21. Liu R, Brown C, Murphy T. Differential regulation of cell proliferation in neurogenic zones in mice lacking cystine transport by xCT. Biochem Biophys Res Commun. 2007;364:528-33 pubmed
    ..Using mice that are homozygous for a function-blocking deletion in xCT (Sut mice), we examined in vivo the role of xCT in cell proliferation in neurogenic regions of the subventricular zone (..
  22. Kobayashi S, Kuwata K, Sugimoto T, Igarashi K, Osaki M, Okada F, et al. Enhanced expression of cystine/glutamate transporter in the lung caused by the oxidative-stress-inducing agent paraquat. Free Radic Biol Med. 2012;53:2197-203 pubmed publisher
    ..The substrate-specific subunit of this transporter, xCT, is strongly induced by various stimuli, including oxidative stress, which suggests that xCT is one of the adaptive ..
  23. Lewerenz J, Sato H, Albrecht P, Henke N, Noack R, Methner A, et al. Mutation of ATF4 mediates resistance of neuronal cell lines against oxidative stress by inducing xCT expression. Cell Death Differ. 2012;19:847-58 pubmed publisher
    ..system x(c)(-), which imports cystine for synthesis of the antioxidant glutathione, and its specific subunit, xCT, are upregulated. (Lewerenz et al., J Neurochem 98(3):916-25)...
  24. Jiang L, Kon N, Li T, Wang S, Su T, Hibshoosh H, et al. Ferroptosis as a p53-mediated activity during tumour suppression. Nature. 2015;520:57-62 pubmed publisher
    ..uptake and sensitizes cells to ferroptosis, a non-apoptotic form of cell death, by repressing expression of SLC7A11, a key component of the cystine/glutamate antiporter...
  25. Mesci P, Zaïdi S, Lobsiger C, Millecamps S, Escartin C, Seilhean D, et al. System xC- is a mediator of microglial function and its deletion slows symptoms in amyotrophic lateral sclerosis mice. Brain. 2015;138:53-68 pubmed publisher
    ..microglia through their system [Formula: see text] (a cystine/glutamate antiporter with the specific subunit xCT/Slc7a11) could contribute to neurodegeneration...
  26. Van Liefferinge J, Bentea E, Demuyser T, Albertini G, Follin Arbelet V, Holmseth S, et al. Comparative analysis of antibodies to xCT (Slc7a11): Forewarned is forearmed. J Comp Neurol. 2016;524:1015-32 pubmed publisher
    ..One important reason for the contradictory findings that have been reported to date is the use of nonspecific anti-xCT (the specific subunit of system Xc-) antibodies. Often studies rely on the predicted molecular weight of 55...
  27. Nguyen T, Wei M. Characterization of melanosomes in murine Hermansky-Pudlak syndrome: mechanisms of hypopigmentation. J Invest Dermatol. 2004;122:452-60 pubmed
  28. Uno K, Takarada T, Takarada Iemata M, Nakamura Y, Fujita H, Hinoi E, et al. Negative regulation of osteoblastogenesis through downregulation of runt-related transcription factor-2 in osteoblastic MC3T3-E1 cells with stable overexpression of the cystine/glutamate antiporter xCT subunit. J Cell Physiol. 2011;226:2953-64 pubmed publisher
    ..role of the antiporter in osteoblastogenesis, in this study, we have established stable transfectants of the xCT subunit of the antiporter in MC3T3-E1 cells...
  29. Nabeyama A, Kurita A, Asano K, Miyake Y, Yasuda T, Miura I, et al. xCT deficiency accelerates chemically induced tumorigenesis. Proc Natl Acad Sci U S A. 2010;107:6436-41 pubmed publisher
    ..Here, we showed that xCT, a component of transport system x(c)(-), was significantly up-regulated in activated infiltrating cells, including ..
  30. Koppula P, Zhang Y, Shi J, Li W, Gan B. The glutamate/cystine antiporter SLC7A11/xCT enhances cancer cell dependency on glucose by exporting glutamate. J Biol Chem. 2017;292:14240-14249 pubmed publisher
    ..The glutamate/cystine antiporter solute carrier family 7 member 11 (SLC7A11, also called xCT) is overexpressed in several cancers...
  31. Jackman N, Melchior S, Hewett J, Hewett S. Non-cell autonomous influence of the astrocyte system xc- on hypoglycaemic neuronal cell death. ASN Neuro. 2012;4: pubmed publisher
    ..plated on top of astrocytes derived from sut mice, which harbour a naturally occurring null mutation in the gene (Slc7a11) that encodes the substrate-specific light chain of system xc- (xCT)...
  32. Li Y, Tan Z, Li Z, Sun Z, Duan S, Li W. Impaired long-term potentiation and long-term memory deficits in xCT-deficient sut mice. Biosci Rep. 2012;32:315-21 pubmed publisher
    b>xCT is the functional subunit of the cystine/glutamate antiporter system xc-, which exchanges intracellular glutamate with extracellular cystine...
  33. Thorn T, He Y, Jackman N, Lobner D, Hewett J, Hewett S. A Cytotoxic, Co-operative Interaction Between Energy Deprivation and Glutamate Release From System xc- Mediates Aglycemic Neuronal Cell Death. ASN Neuro. 2015;7: pubmed publisher
  34. Ishimoto T, Nagano O, Yae T, Tamada M, Motohara T, Oshima H, et al. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth. Cancer Cell. 2011;19:387-400 pubmed publisher
    ..Here, we show that a CD44 variant (CD44v) interacts with xCT, a glutamate-cystine transporter, and controls the intracellular level of reduced glutathione (GSH)...
  35. Shi J, He Y, Hewett S, Hewett J. Interleukin 1β Regulation of the System xc- Substrate-specific Subunit, xCT, in Primary Mouse Astrocytes Involves the RNA-binding Protein HuR. J Biol Chem. 2016;291:1643-51 pubmed publisher
    ..the activity of system xc(-) in CNS astrocytes secondary to an up-regulation of its substrate-specific light chain, xCT, and that this occurs, in part, at the level of transcription...
  36. Ottestad Hansen S, Hu Q, Follin Arbelet V, Bentea E, Sato H, Massie A, et al. The cystine-glutamate exchanger (xCT, Slc7a11) is expressed in significant concentrations in a subpopulation of astrocytes in the mouse brain. Glia. 2018;66:951-970 pubmed publisher
    The cystine-glutamate exchanger (xCT) promotes glutathione synthesis by catalyzing cystine uptake and glutamate release...
  37. Hsieh C, Lin Y, Chen W, Huang Y, Chang C, Cheng F, et al. HIF-1? triggers long-lasting glutamate excitotoxicity via system xc- in cerebral ischaemia-reperfusion. J Pathol. 2017;241:337-349 pubmed publisher
    ..we found that HIF-1? mainly regulates the cystine-glutamate transporter (system xc- ) subunit xCT by directly binding to its promoter; xCT and its function are up-regulated in the ischaemic brains of rodents and ..
  38. Evonuk K, Baker B, Doyle R, Moseley C, Sestero C, Johnston B, et al. Inhibition of System Xc(-) Transporter Attenuates Autoimmune Inflammatory Demyelination. J Immunol. 2015;195:450-463 pubmed publisher
    ..Mice harboring a Slc7a11 (xCT) mutation that inactivated system Xc(-) were resistant to EAE, corroborating a central role for system Xc(-) ..
  39. Wada T, Ishimoto T, Seishima R, Tsuchihashi K, Yoshikawa M, Oshima H, et al. Functional role of CD44v-xCT system in the development of spasmolytic polypeptide-expressing metaplasia. Cancer Sci. 2013;104:1323-9 pubmed publisher
    ..We recently found that CD44v interacts with and stabilizes xCT, a subunit of the cystine transporter system xc(-), in cancer cells and thereby increases cystine uptake and ..
  40. Takarada Iemata M, Takarada T, Nakamura Y, Nakatani E, Hori O, Yoneda Y. Glutamate preferentially suppresses osteoblastogenesis than adipogenesis through the cystine/glutamate antiporter in mesenchymal stem cells. J Cell Physiol. 2011;226:652-65 pubmed publisher
  41. Liu X, Rush T, Zapata J, Lobner D. beta-N-methylamino-l-alanine induces oxidative stress and glutamate release through action on system Xc(-). Exp Neurol. 2009;217:429-33 pubmed publisher
    ..The multiple mechanisms of BMAA toxicity, particularly the depletion of glutathione and enhanced oxidative stress, may account for its ability to induce complex neurodegenerative diseases. ..
  42. Huizing M, Anikster Y, White J, Gahl W. Characterization of the murine gene corresponding to human Hermansky-Pudlak syndrome type 3: exclusion of the Subtle gray (sut) locus. Mol Genet Metab. 2001;74:217-25 pubmed
    ..Furthermore, subtle gray exhibits a normal contingent of platelet dense bodies. Together, these data eliminate subtle gray as a murine model for HPS-3 disease and suggest that other mouse models be examined. ..
  43. Merckx E, Albertini G, Paterka M, Jensen C, Albrecht P, Dietrich M, et al. Absence of system xc- on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis. J Neuroinflammation. 2017;14:9 pubmed publisher
    ..Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system xc-, as well as of regulators of xCT transcription, in the ..
  44. Gnana Prakasam J, Thangaraju M, Liu K, Ha Y, Martin P, Smith S, et al. Absence of iron-regulatory protein Hfe results in hyperproliferation of retinal pigment epithelium: role of cystine/glutamate exchanger. Biochem J. 2009;424:243-52 pubmed publisher
    ..One of the genes up-regulated in Hfe-/- RPE cells was Slc7a11 (where Slc is solute carrier) which codes for the 'transporter proper' xCT in the heterodimeric cystine/glutamate ..
  45. Cai Y, Yang Q, Liao M, Wang H, Zhang C, Nambi S, et al. xCT increases tuberculosis susceptibility by regulating antimicrobial function and inflammation. Oncotarget. 2016;7:31001-13 pubmed publisher
    ..System xc-, a cystine-glutamate transporter, which consists of xCT and CD98, influences many ROS-dependent pathways by regulating the production of the antioxidant glutathione...
  46. D Elia M, Patenaude J, Dupras C, Bernier J. Burn injury induces the expression of cystine/glutamate transporter (x(c)(-)) in mouse T cells. Immunol Lett. 2009;125:137-44 pubmed publisher
    System x(c)(-) transporter, formed by the association of CD98 and xCT proteins, regulates the import of cystine into cells and is poorly expressed in T lymphocytes...
  47. Chen D, Tavana O, Chu B, Erber L, Chen Y, Baer R, et al. NRF2 Is a Major Target of ARF in p53-Independent Tumor Suppression. Mol Cell. 2017;68:224-232.e4 pubmed publisher
    ..ARF inhibits the ability of NRF2 to transcriptionally activate its target genes, including SLC7A11, a component of the cystine/glutamate antiporter that regulates reactive oxygen species (ROS)-induced ferroptosis...
  48. Williams L, Featherstone D. Regulation of hippocampal synaptic strength by glial xCT. J Neurosci. 2014;34:16093-102 pubmed publisher
    Most extracellular glutamate in the brain is released by xCT, a glial antiporter that exports glutamate and imports cystine. The function of xCT, and extracellular glutamate in general, remains unclear...
  49. Sims B, Clarke M, Francillion L, Kindred E, Hopkins E, Sontheimer H. Hypoxic preconditioning involves system Xc- regulation in mouse neural stem cells. Stem Cell Res. 2012;8:285-91 pubmed publisher
    ..The mRNA for the regulatory subunit of system Xc-, xCT, and the xCT/actin ratio were also increased under hypoxic conditions...
  50. Shibasaki T, Iuchi Y, Okada F, Kuwata K, Yamanobe T, Bannai S, et al. Aggravation of ischemia-reperfusion-triggered acute renal failure in xCT-deficient mice. Arch Biochem Biophys. 2009;490:63-9 pubmed publisher
    This study examined the question of whether deficiency of xCT, a cystine-transporter gene, exacerbates ischemia-reperfusion-induced acute renal failure (ARF)...
  51. Swank R, Novak E, McGarry M, Rusiniak M, Feng L. Mouse models of Hermansky Pudlak syndrome: a review. Pigment Cell Res. 1998;11:60-80 pubmed