Inhibition of D-serine accumulation in the Xenopus oocyte by expression of the rat ortholog of human 3'-phosphoadenosine 5'-phosphosulfate transporter gene isolated from the neocortex as D-serine modulator-1.
D-serine in mammalian brains has been suggested to be an endogenous co-agonist of the NMDA-type glutamate receptor. We have explored the molecules regulating D-serine uptake and release from the rat neocortex cDNA library using a Xenopus oocyte expression system, and isolated a cDNA clone designated as dsm-1 (D-serine modulator-1) encoding a protein that reduces the accumulation of D-serine to the oocyte. dsm-1 is the rat orthologue of the human 3'-phosphoadenosine 5'-phosphosulfate transporter 1 (PAPST1) gene. The hydropathy analysis of the deduced amino acid sequence of the Dsm-1 protein predicts the 10 transmembrane domains with a long hydrophobic stretch in the C-terminal like some amino acid transporters. The dsm-1 mRNA is predominantly expressed in the forebrain areas that are enriched with D-serine and NMDA receptors, and in the liver. The transient expression of dsm-1 in COS-7 cells demonstrates a partially Golgi apparatus-related punctuate distribution throughout the cytoplasm with a concentration near the nucleus. dsm-1-expressing oocytes diminishes the sodium-dependent and -independent accumulation of D-serine and the basal levels of the intrinsic D-serine and increases the rate of release of the pre-loaded D-serine. These findings indicate that dsm-1 may, at least in part, be involved in the D-serine translocation across the vesicular or plasma membranes in the brain, and thereby control the extra- and intracellular contents of D-serine.
Shimazu
Dai
D
Section of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, Tokyo, Japan.
Yamamoto
Naoki
N
Umino
Asami
A
Ishii
Sumikazu
S
Sakurai
Shin-ichiro
S
Nishikawa
Toru
T
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D019556:COS Cells; D002522:Chlorocebus aethiops; D002851:Chromatography, High Pressure Liquid; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D026901:Membrane Transport Proteins / Q000235:genetics*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D019579:Neocortex / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012694:Serine / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D000076988:Sulfate Transporters; D014981:Xenopus
D000596:Amino Acids; D018076:DNA, Complementary; D026901:Membrane Transport Proteins; C476248:SLC35B2 protein, human; D000076988:Sulfate Transporters; D012694:Serine