ArticlePloS one2010
A single amino acid change converts the sugar sensor SGLT3 into a sugar transporter.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 69 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Human Glucose Transporters in Health and Selected Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- High-Fructose-Induced Salt-Sensitive Hypertension: The Potential Benefit of SGLT4 or SGLT5 Modulation.Nutrients · 2025Review
- Molecular mechanisms and computational insights into human SGLTs: advancing toward selective SGLT1 inhibition.Frontiers in molecular biosciences · 2025Review
- A sodium-dependent trehalose transporter contributes to anhydrobiosis in insect cell line, Pv11.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Pharmacogenetics of sodium-glucose co-transporter-2 inhibitors: Validation of a sex-agnostic pharmacodynamic biomarker.Diabetes, obesity & metabolism · 2023Article
- Pharmacogenetics of SGLT2 Inhibitors: Validation of a sex-agnostic pharmacodynamic biomarker.medRxiv : the preprint server for health sciences · 2023Article
- The influence of SARS-CoV-2 infection on expression of drug-metabolizing enzymes and transporters in a hACE2 murine model.Pharmacology research & perspectives · 2023Article
- Unlocking the Full Potential of SGLT2 Inhibitors: Expanding Applications beyond Glycemic Control.International journal of molecular sciences · 2023Review
- Glucose transporters as markers of diagnosis and prognosis in cancer diseases.Oncology reviews · 2022Article
- Human Glucose Transporters in Renal Glucose Homeostasis.International journal of molecular sciences · 2021Review
- Glucose Transporters as a Target for Anticancer Therapy.Cancers · 2021Review
- Brain Glucose Transporters: Role in Pathogenesis and Potential Targets for the Treatment of Alzheimer's Disease.International journal of molecular sciences · 2021Review
- Sodium-coupled glucose transport, the SLC5 family, and therapeutically relevant inhibitors: from molecular discovery to clinical application.Pflugers Archiv : European journal of physiology · 2020Review
- Comparison of intestinal glucose flux and electrogenic current demonstrates two absorptive pathways in pig and one in Nile tilapia and rainbow trout.American journal of physiology. Regulatory, integrative and comparative physiology · 2020Article
- Sodium-Glucose Cotransporter 2 Inhibitors: A Case Study in Translational Research.Diabetes · 2019 · on this mapReview
- Brain Glucose-Sensing Mechanism and Energy Homeostasis.Molecular neurobiology · 2019Review
- Multiple Transceptors for Macro- and Micro-Nutrients Control Diverse Cellular Properties Through the PKA Pathway in Yeast: A Paradigm for the Rapidly Expanding World of Eukaryotic Nutrient Transceptors Up to Those in Human Cells.Frontiers in pharmacology · 2018Review
- Distribution of glucose transporters in renal diseases.Journal of biomedical science · 2017Review
- Achieving global perfect homeostasis through transporter regulation.PLoS computational biology · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSodium-glucose cotransporter proteins (SGLT) belong to the SLC5A family, characterized by the cotransport of Na(+) with solute. SGLT1 is responsible for intestinal glucose absorption. Until recently the only role described for SGLT proteins was to transport sugar with Na(+). However, human SGLT3 (hSGLT3) does not transport sugar but causes depolarization of the plasma membrane when expressed in Xenopus oocytes. For this reason SGLT3 was suggested to be a sugar sensor rather than a transporter. Despite 70% amino acid identity between hSGLT3 and hSGLT1, their sugar transport, apparent sugar affinities, and sugar specificity differ greatly. Residue 457 is important for the function of SGLT1 and mutation at this position in hSGLT1 causes glucose-galactose malabsorption. Moreover, the crystal structure of vibrio SGLT reveals that the residue corresponding to 457 interacts directly with the sugar molecule. We thus wondered if this residue could account for some of the functional differences between SGLT1 and SGLT3. METHODOLOGY/PRINCIPAL
findingsWe mutated the glutamate at position 457 in hSGLT3 to glutamine, the amino acid present in all SGLT1 proteins, and characterized the mutant. Surprisingly, we found that E457Q-hSGLT3 transported sugar, had the same stoichiometry as SGLT1, and that the sugar specificity and apparent affinities for most sugars were similar to hSGLT1. We also show that SGLT3 functions as a sugar sensor in a living organism. We expressed hSGLT3 and E457Q-hSGLT3 in C. elegans sensory neurons and found that animals sensed glucose in an hSGLT3-dependent manner. CONCLUSIONS/SIGNIFICANCE: In summary, we demonstrate that hSGLT3 functions as a sugar sensor in vivo and that mutating a single amino acid converts this sugar sensor into a sugar transporter similar to SGLT1.
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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.