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

• Published in: Journal of neurochemistry 2006-01, Vol.96 (1), p.30-42
• Main Authors: Shimazu, Dai, Yamamoto, Naoki, Umino, Asami, Ishii, Sumikazu, Sakurai, Shin‐ichiro, Nishikawa, Toru
• Format: Article
• Language: English
• Subjects: 3′‐phsophoadenosine 5′‐phosphosulfate; Amino Acid Sequence; Amino Acids - analysis; Amino Acids - metabolism; Animals; Biological and medical sciences; Blotting, Northern; Blotting, Southern; brain; Cercopithecus aethiops; Chromatography, High Pressure Liquid; COS Cells; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA, Complementary - biosynthesis; DNA, Complementary - genetics; d‐serine; d‐serine modulator‐1 gene; Fundamental and applied biological sciences. Psychology; Gene expression; Humans; In Situ Hybridization; Medical sciences; Membrane Transport Proteins - genetics; Microscopy, Fluorescence; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Neocortex - metabolism; Neurology; NMDA receptor; Oocytes - metabolism; Rats; Reverse Transcriptase Polymerase Chain Reaction; Serine - metabolism; Subcellular Fractions - metabolism; transporter; Xenopus; Xenopus oocyte
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2005.03501.x

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.