The apical localization of SGLT1 glucose transporter is determined by the short amino acid sequence in its N-terminal domain.
SGLT1, an isoform of Na+-dependent glucose cotransporters, is localized at the apical plasma membrane in the epithelial cells of the small intestine and the kidney, where it plays a pivotal role in the absorption and reabsorption of sugars, respectively. To search the domain responsible for the apical localization of SGLT1, we constructed an N-terminal deletion clone series of rat SGLT1 and analyzed the localization of the respective products in Madin-Darby canine kidney (MDCK) cells. The products of N-terminal deletion clones up to the 19th amino acid were localized at the apical plasma membrane, whereas the products of N-terminal 20- and 23-amino-acid deletion clones were localized along the entire plasma membrane. Since single-amino-acid mutations of either D28N or D28G in the N-terminal domain give rise to glucose/galactose malabsorption disease, we examined the localization of these mutants. The products of D28N and D28G clones were localized in the cytoplasm, showing that the aspartic acid-28 may be essential for the delivery of SGLT1 to the plasma membrane. These results suggest that a short amino acid sequence of the N-terminal domain of SGLT1 plays important roles in plasma membrane targeting and specific apical localization of the protein.
Suzuki
T
T
Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan. suzutake@showa.gunma-u.ac.jp
Fujikura
K
K
Koyama
H
H
Matsuzaki
T
T
Takahashi
Y
Y
Takata
K
K
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004285:Dogs; D008562:Membrane Glycoproteins / Q000032:analysis*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000032:analysis*; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments; D017434:Protein Structure, Tertiary; D051381:Rats; D051269:Sodium-Glucose Transporter 1; D014162:Transfection
D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D010446:Peptide Fragments; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1