ArticleThe Journal of biological chemistry2015
ATP-binding Cassette Subfamily C Member 5 (ABCC5) Functions as an Efflux Transporter of Glutamate Conjugates and Analogs.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 66 citations in OpenAlex.
- An Emerging Paradigm for ABCC5/MRP5 Function in Human Physiology.International journal of molecular sciences · 2025Review
- The murine ATP-binding cassette transporter C5 (Abcc5/MRP5/cMOAT) plays a role in memory consolidation, circadian rhythm regulation and glutamatergic signalling.Translational psychiatry · 2025Article
- SNP array analysis facilitates the identification of novel chromosomal alterations associated with disease and SNPs related to adverse drug reactions in neuroblastoma.Oncology letters · 2025Article
- The disturbance of ABC transporters in patients with dengue fever: integration of metabolomics and transcriptomics.Frontiers in cellular and infection microbiology · 2025Article
- Obesity-related drug transporter expression alterations in human liver and kidneys.Pharmacological reports : PR · 2024Article
- Cellular and molecular mechanisms of aspartoacylase and its role in Canavan disease.Cell & bioscience · 2024Review
- Roles and Mechanisms of Ferroptosis in Sorafenib Resistance for Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2024Review
- Role of ABCC5 in cancer drug resistance and its potential as a therapeutic target.Frontiers in cell and developmental biology · 2024Review
- Enhancing of cerebral Abeta clearance by modulation of ABC transporter expression: a review of experimental approaches.Frontiers in aging neuroscience · 2024Review
- Ferroptosis as a potential target for cancer therapy.Cell death & disease · 2023Review
- Notes from the Underground: Heme Homeostasis inBiomolecules · 2023Review
- Mechanism of sorafenib resistance associated with ferroptosis in HCC.Frontiers in pharmacology · 2023Review
- Genome-Wide Identification, Characterisation and Phylogenetic Analysis of 52 Striped Catfish (Tropical life sciences research · 2022Article
- Effects of Acute and Chronic Resistance Exercise on the Skeletal Muscle Metabolome.Metabolites · 2022Article
- Non-drug efflux function of ABCC5 promotes enzalutamide resistance in castration-resistant prostate cancer via upregulation of P65/AR-V7.Cell death discovery · 2022Article
- MRP5 and MRP9 play a concerted role in male reproduction and mitochondrial function.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The Emerging Roles of Circular RNAs in the Chemoresistance of Gastrointestinal Cancer.Frontiers in cell and developmental biology · 2022Review
- System XFrontiers in pharmacology · 2022Review
- The molecular evolution of function in the CFTR chloride channel.The Journal of general physiology · 2021Article
- Alteration of payload in extracellular vesicles by crosstalk with mesenchymal stem cells from different origin.Journal of nanobiotechnology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ubiquitous efflux transporter ABCC5 (ATP-binding cassette subfamily C member 5) is present at high levels in the blood-brain barrier, neurons, and glia, but its in vivo substrates and function are not known. Using untargeted metabolomic screens, we show that Abcc5(-/-) mice accumulate endogenous glutamate conjugates in several tissues, but brain in particular. The abundant neurotransmitter N-acetylaspartylglutamate was 2.4-fold higher in Abcc5(-/-) brain. The metabolites that accumulated in Abcc5(-/-) tissues were depleted in cultured cells that overexpressed human ABCC5. In a vesicular membrane transport assay, ABCC5 also transported exogenous glutamate analogs, like the classic excitotoxic neurotoxins kainic acid, domoic acid, and NMDA; the therapeutic glutamate analog ZJ43; and, as previously shown, the anti-cancer drug methotrexate. Glutamate conjugates and analogs are of physiological relevance because they can affect the function of glutamate, the principal excitatory neurotransmitter in the brain. After CO2 asphyxiation, several immediate early genes were expressed at lower levels in Abcc5(-/-) brains than in wild type brains, suggesting altered glutamate signaling. Our results show that ABCC5 is a general glutamate conjugate and analog transporter that affects the disposition of endogenous metabolites, toxins, and drugs.
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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.