Disease-associated Glut1 single amino acid substitute mutations S66F, R126C, and T295M constitute Glut1-deficiency states in vitro
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香港中文大學研究人員

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摘要Glucose transporter type 1 deficiency syndrome (Glut1DS) is the result of autosomal-dominant loss-offunction 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 Glut I functional deticits 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) V-max but not K-m. 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. (c) 2006 Elsevier Inc. All rights reserved.
著者Wong HY, Law PY, Ho YY
期刊名稱Molecular Genetics and Metabolism
出版年份2007
月份2
日期1
卷號90
期次2
出版社ACADEMIC PRESS INC ELSEVIER SCIENCE
頁次193 - 198
國際標準期刊號1096-7192
電子國際標準期刊號1096-7206
語言英式英語
關鍵詞blood-brain barrier; epilepsy; Glut1; Glut1-deficiency syndrome; green fluorescent protein
Web of Science 學科類別BIOCHEMISTRY & MOLECULAR BIOLOGY; Endocrinology & Metabolism; Genetics & Heredity; GENETICS & HEREDITY; Medicine, Research & Experimental; MEDICINE, RESEARCH & EXPERIMENTAL; Research & Experimental Medicine

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