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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
Author(s) -
Shimazu Dai,
Yamamoto Naoki,
Umino Asami,
Ishii Sumikazu,
Sakurai Shinichiro,
Nishikawa Toru
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03501.x
Subject(s) - serine , biology , xenopus , biochemistry , neocortex , transmembrane protein , amino acid , complementary dna , transmembrane domain , microbiology and biotechnology , receptor , phosphorylation , gene , neuroscience
Abstract 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.