Transport of D-serine via the amino acid transporter ATB(0,+) expressed in the colon.
D-Serine, synthesized endogenously in the brain, is an important modulator of glutamatergic neurotransmission. Since colonic bacteria produce D-serine, we asked the question whether there are transport mechanisms in the colon that might make this exogenously produced D-serine available to the host. Here we identify for the first time an amino acid transporter in the intestine for high-affinity active transport of D-serine. This transporter, called ATB(0,+), is a Na(+)- and Cl(-)-coupled transporter for L-enantiomers of neutral and cationic amino acids. Here we demonstrate that ATB(0,+) is also capable of mediating the Na(+)- and Cl(-)-coupled transport of D-serine. The affinity of ATB(0,+) for L-serine and D-serine is similar, the K(t) value for the two enantiomers being approximately 150 microM. In addition to D-serine, ATB(0,+) transports D-alanine, D-methionine, D-leucine, and D-tryptophan. However, several other neutral and cationic amino acids that are transportable substrates for ATB(0,+) as L-enantiomers are not transported when presented as D-enantiomers. ATB(0,+) is expressed in the intestinal tract, interestingly not in the proximal intestine but in the distal intestine. Expression is most predominant in the colon where the transporter is localized to the luminal membrane of colonocytes, making this transporter uniquely suitable for absorption of bacteria-derived D-serine.
Hatanaka
Takahiro
T
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia 30912, USA.
Huang
Wei
W
Nakanishi
Takeo
T
Bridges
Christy C
CC
Smith
Sylvia B
SB
Prasad
Puttur D
PD
Ganapathy
Malliga E
ME
Ganapathy
Vadivel
V
D026923:Amino Acid Transport Systems, Basic / Q000235:genetics / Q000502:physiology; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics / Q000502:physiology*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D003106:Colon / Q000033:anatomy & histology / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009865:Oocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012694:Serine / Q000378:metabolism*; D014981:Xenopus
D026923:Amino Acid Transport Systems, Basic; D026921:Amino Acid Transport Systems, Neutral; D000596:Amino Acids; D012333:RNA, Messenger; D012694:Serine