ArticleThe Journal of biological chemistry2009
Oligomeric structure of the human reduced folate carrier: identification of homo-oligomers and dominant-negative effects on carrier expression and function.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- A dominant negative heterozygous G87R mutation in the zinc transporter, ZnT-2 (SLC30A2), results in transient neonatal zinc deficiency.The Journal of biological chemistry · 2012Trial
- Biology and therapeutic applications of the proton-coupled folate transporter.Expert opinion on drug metabolism & toxicology · 2022Article
- The evolving biology of the proton-coupled folate transporter: New insights into regulation, structure, and mechanism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Review
- Folate transporter dynamics and therapy with classic and tumor-targeted antifolates.Scientific reports · 2021Article
- Structural basis of methotrexate and pemetrexed action on serine hydroxymethyltransferases revealed using plant models.Scientific reports · 2019Article
- Molecular Mechanism Underlying the Plant NRT1.1 Dual-Affinity Nitrate Transporter.Frontiers in physiology · 2015Review
- Post-transcriptional regulation of the human reduced folate carrier as a novel adaptive mechanism in response to folate excess or deficiency.Bioscience reports · 2014Article
- The major facilitative folate transporters solute carrier 19A1 and solute carrier 46A1: biology and role in antifolate chemotherapy of cancer.Drug metabolism and disposition: the biological fate of chemicals · 2014Review
- Biology of the major facilitative folate transporters SLC19A1 and SLC46A1.Current topics in membranes · 2014Review
- Cerebral folate receptor autoantibodies in autism spectrum disorder.Molecular psychiatry · 2013Article
- The human proton-coupled folate transporter: Biology and therapeutic applications to cancer.Cancer biology & therapy · 2012Review
- Identification and functional impact of homo-oligomers of the human proton-coupled folate transporter.The Journal of biological chemistry · 2012Article
- Mechanisms of membrane transport of folates into cells and across epithelia.Annual review of nutrition · 2011Review
- Substrate-specific binding and conformational changes involving Ser313 and transmembrane domain 8 of the human reduced folate carrier, as determined by site-directed mutagenesis and protein cross-linking.The Biochemical journal · 2010Article
- Association of folate receptor (FOLR1, FOLR2, FOLR3) and reduced folate carrier (SLC19A1) genes with meningomyelocele.Birth defects research. Part A, Clinical and molecular teratology · 2010Article
- Identification of the minimal functional unit of the homo-oligomeric human reduced folate carrier.The Journal of biological chemistry · 2010Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The ubiquitously expressed reduced folate carrier (RFC) is the major transport system for folate cofactors in mammalian cells and tissues. Previous considerations of RFC structure and mechanism were based on the notion that RFC monomers were sufficient to mediate transport of folate and antifolate substrates. The present study examines the possibility that human RFC (hRFC) exists as higher order homo-oligomers. By chemical cross-linking, transiently expressed hRFC in hRFC-null HeLa (R5) cells with the homobifunctional cross-linker 1,3-propanediyl bis-methanethiosulfonate and Western blotting, hRFC species with molecular masses of hRFC homo-oligomers were identified. Hemagglutinin- and Myc epitope-tagged hRFC proteins expressed in R5 cells were co-immunoprecipitated from both membrane particulate and surface-enriched membrane fractions, indicating that oligomeric hRFC is expressed at the cell surface. By co-expression of wild type and inactive mutant S138C hRFCs, combined with surface biotinylation and confocal microscopy, a dominant-negative phenotype was demonstrated involving greatly decreased cell surface expression of both mutant and wild type carrier caused by impaired intracellular trafficking. For another hRFC mutant (R373A), expression of oligomeric wild type-mutant hRFC was accompanied by a significant and disproportionate loss of wild type activity unrelated to the level of surface carrier. Collectively, our results demonstrate the existence of hRFC homo-oligomers. They also establish the likely importance of these higher order hRFC structures to intracellular trafficking and carrier function.
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Registered trials
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.