SLC5A9/SGLT4, a new Na+-dependent glucose transporter, is an essential transporter for mannose, 1,5-anhydro-D-glucitol, and fructose.
We isolated a cDNA clone of SLC5A9/SGLT4 from human small intestinal full-length cDNA libraries, and functionally characterized it in vitro. The messenger RNA encoding SGLT4 was mainly expressed in the small intestine and kidney, among the human tissues tested. COS-7 cells transiently expressing SGLT4 exhibited Na(+)-dependent alpha-methyl-D-glucopyranoside (AMG) transport activity with an apparent K(m) of 2.6 mM, suggesting that SGLT4 is a low affinity-type transporter. The rank order of naturally occurring sugar analogs for the inhibition of AMG transport was: D-mannose (Man) >> D-glucose (Glc) > D-fructose (Fru) = 1,5-anhydro-D-glucitol (1,5AG) > D-galactose (Gal). Recognition of Man as a substrate was confirmed by direct uptake of Man into the cell. COS-7 cells expressing a putative murine SGLT4 ortholog showed similar Na(+)-dependent AMG transport activity and a similar deduced substrate specificity. These results suggest that SGLT4 would have unique physiological functions (i.e., absorption and/or reabsorption of Man, 1,5AG, and Fru, in addition to Glc).
Tazawa
Shigeki
S
Discovery Research II, R&D, Kissei Pharmaceutical Co. Ltd., 4365-1 Kashiwabara, Hotaka, Minamiazumi, Nagano, 399-8304, Japan.
Yamato
Tokuhisa
T
Fujikura
Hideki
H
Hiratochi
Masahiro
M
Itoh
Fumiaki
F
Tomae
Masaki
M
Takemura
Yukiko
Y
Maruyama
Hidetoshi
H
Sugiyama
Tomoyasu
T
Wakamatsu
Ai
A
Isogai
Takao
T
Isaji
Masayuki
M
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D003847:Deoxyglucose / Q000378:metabolism*; D005632:Fructose / Q000378:metabolism*; D006801:Humans; D008358:Mannose / Q000378:metabolism*; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051297:Sodium-Glucose Transporter 2
D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D005632:Fructose; C006584:1,5-anhydroglucitol; D003847:Deoxyglucose; D008358:Mannose