| Disease-associated Glut1 single amino acid substitute mutations S66F, R126C, and T295M constitute Glut1-deficiency states in vitro. | |
| | |
MedLine Citation:
|
PMID: 17052934 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Glucose transporter type 1 deficiency syndrome (Glut1DS) is the result of autosomal-dominant loss-of-function mutation of the glucose transporter type 1 gene (GLUT1) leading to brain energy failure and epileptic encephalopathy. In this study, the protein products of the Glut1DS-associated GLUT1 missense mutations, S66F, R126C, and T295M, were characterized using the Glut1-green fluorescent protein (GFP) fusion expressed in CHO cells. Glut1-GFP expression was confirmed by Western blot and confocal microscopy. The applicability of this Glut1-GFP expression model in reporting Glut1 functional deficits was validated by re-confirming the glucose transport defects of the previously reported pathogenic mutations R126H, R126L, and R333W. While S66F, R126C, and T295M mutants were expressed and targeted to the cell membrane, these Glut1 mutants have significantly diminished membrane association and glucose transport activity (p<0.05) relative to the wild-type Glut1 protein. Consistent with the reduced Glut1 membrane association, glucose transport kinetics studies showed that S66F, R126C, and T295M mutants have significantly reduced (p<0.05) Vmax but not Km. Thus, Glut1 single amino acid substitute mutants S66F, R126C, and T295M impair glucose transport function and constitute Glut1-deficiency states in vitro. These results support the pathogenicity of Glut1 S66F, R126C, and T295M in vivo. |
| | |
Authors:
|
H Y Wong; P Y Law; Y Y Ho |
Related Documents
:
|
21445964 - Establishment of conditional reporter mouse lines at rosa26 locus for live cell imaging. 19368904 - A high molecular arabinogalactan from ribes nigrum l.: influence on cell physiology of ... 15123614 - Loss of srf-3-encoded nucleotide sugar transporter activity in caenorhabditis elegans a... 7550244 - Molecular cloning of a putative na(+)-k(+)-2cl- cotransporter from the malpighian tubul... 3548034 - Characterization of morphogenetic intermediates and progeny of normal and alkylated bac... 2471974 - Isolation and dna sequence of a cdna clone encoding a lymphocyte adhesion receptor for ... |
Publication Detail:
|
Type: Journal Article Date: 2006-10-18 |
Journal Detail:
|
Title: Molecular genetics and metabolism Volume: 90 ISSN: 1096-7192 ISO Abbreviation: Mol. Genet. Metab. Publication Date: 2007 Feb |
Date Detail:
|
Created Date: 2007-01-22 Completed Date: 2007-03-29 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9805456 Medline TA: Mol Genet Metab Country: United States |
Other Details:
|
Languages: eng Pagination: 193-8 Citation Subset: IM |
Affiliation:
|
Molecular Biotechnology Program, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Substitution* Animals Biological Transport CHO Cells Carbohydrate Metabolism, Inborn Errors / genetics* Cricetinae Cricetulus Glucose / metabolism Glucose Transporter Type 1 / genetics*, metabolism* Green Fluorescent Proteins / genetics, metabolism Humans Mutation* |
| Chemical | |
Reg. No./Substance:
|
0/Glucose Transporter Type 1; 0/SLC2A1 protein, human; 147336-22-9/Green Fluorescent Proteins; 50-99-7/Glucose |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Data correction strategy for metabolomics analysis using gas chromatography-mass spectrometry.
Next Document: Results of magnetic resonance imaging in 14 cats with meningoencephalitis.