Functional analysis of a triplet deletion in the gene encoding the sodium glucose transporter 3, a potential risk factor for ADHD
Schäfer N., Friedrich M., Jorgensen M. E., Kollert Z. I. E`., Koepsell H., Wischmeyer E., Lesh K. Yu., Geiger D., Döring F.
PLoS ONE
Vol.13, Issue10, Num.e0205109
Опубликовано: 2018
Тип ресурса: Статья
DOI:10.1371/journal.pone.0205109
Аннотация:
Sodium-glucose transporters (SGLT) belong to the solute carrier 5 family, which is characterized by sodium dependent transport of sugars and other solutes. In contrast, the human SGLT3 (hSGLT3) isoform, encoded by SLC5A4, acts as a glucose sensor that does not transport sugar but induces membrane depolarization by Na+ currents upon ligand binding. Whole-exome sequencing (WES) of several extended pedigrees with high density of attention- deficit/hyperactivity disorder (ADHD) identified a triplet ATG deletion in SLC5A4 leading to a single amino acid loss (ΔM500) in the hSGLT3 protein imperfectly co-segregating with the clinical phenotype of ADHD. Since mutations in homologous domains of hSGLT1 and hSGLT2 were found to affect intestinal and renal function, respectively, we analyzed the functional properties of hSGLT3[wt] and [ΔM500] by voltage clamp and current clamp recordings from cRNA-injected Xenopus laevis oocytes. The cation conductance of hSGLT3[wt] was activated by application of
Ключевые слова:
1 deoxynojirimycin; glucose; sodium glucose cotransporter; sodium glucose cotransporter 1; sodium glucose transporter 3; unclassified drug; yellow fluorescent protein; SLC5A4 protein, human; sodium; sodium glucose cotransporter; amino acid analysis; animal cell; Article; attention deficit disorder; cell membrane depolarization; clinical article; confocal microscopy; controlled study; current clamp technique; female; fluorescence analysis; gene activation; gene deletion; gene expression; gene function; gene fusion; gene location; gene loss; gene structure; gene targeting; gene transfer; genetic analysis; genetic code; genetic risk; genetic variability; heterozygote; human; ion transport; male; membrane potential; nonhuman; oocyte; phenotype; risk factor; sequence homology; SGLT1 gene; SGLT3 gene; SLC5A4 gene; sodium conductance; voltage clamp technique; whole exome sequencing; wild type; Xenopus laevis; animal; attention deficit disorder; cell membrane; chemical structure; family; genet
Язык текста: Английский
ISSN: 1932-6203
Schäfer N.
Friedrich M.
Jorgensen M. E.
Kollert Z. I. E`. Zina Ivonna E`l`frida 1985-
Koepsell H.
Wischmeyer E.
Lesh K. Yu. Klaus-Peter Yulius 1957-
Geiger D.
Döring F.
Счäфер Н.
Фриедрич М.
Йоргенсен М. Е.
Коллерт З. И. Э. Зина Ивонна Эльфрида 1985-
Коепселл Х.
Wисчмеьер Е.
Леш К. Ю. Клаус-Петер Юлиус 1957-
Геигер Д.
Дöринг Ф.
Functional analysis of a triplet deletion in the gene encoding the sodium glucose transporter 3, a potential risk factor for ADHD
Текст визуальный непосредственный
PLoS ONE
Vol.13, Issue10 Num.e0205109
2018
Статья
1 deoxynojirimycin glucose sodium glucose cotransporter sodium glucose cotransporter 1 sodium glucose transporter 3 unclassified drug yellow fluorescent protein SLC5A4 protein, human sodium sodium glucose cotransporter amino acid analysis animal cell Article attention deficit disorder cell membrane depolarization clinical article confocal microscopy controlled study current clamp technique female fluorescence analysis gene activation gene deletion gene expression gene function gene fusion gene location gene loss gene structure gene targeting gene transfer genetic analysis genetic code genetic risk genetic variability heterozygote human ion transport male membrane potential nonhuman oocyte phenotype risk factor sequence homology SGLT1 gene SGLT3 gene SLC5A4 gene sodium conductance voltage clamp technique whole exome sequencing wild type Xenopus laevis animal attention deficit disorder cell membrane chemical structure family genet
Sodium-glucose transporters (SGLT) belong to the solute carrier 5 family, which is characterized by sodium dependent transport of sugars and other solutes. In contrast, the human SGLT3 (hSGLT3) isoform, encoded by SLC5A4, acts as a glucose sensor that does not transport sugar but induces membrane depolarization by Na+ currents upon ligand binding. Whole-exome sequencing (WES) of several extended pedigrees with high density of attention- deficit/hyperactivity disorder (ADHD) identified a triplet ATG deletion in SLC5A4 leading to a single amino acid loss (ΔM500) in the hSGLT3 protein imperfectly co-segregating with the clinical phenotype of ADHD. Since mutations in homologous domains of hSGLT1 and hSGLT2 were found to affect intestinal and renal function, respectively, we analyzed the functional properties of hSGLT3[wt] and [ΔM500] by voltage clamp and current clamp recordings from cRNA-injected Xenopus laevis oocytes. The cation conductance of hSGLT3[wt] was activated by application of