The alanine-serine-cysteine-1 (Asc-1) transporter controls glycine levels in the brain and is required for glycinergic inhibitory transmission

Hazem Safory, Samah Neame, Yoav Shulman, Salman Zubedat, Inna Radzishevsky, Dina Rosenberg, Hagit Sason, Simone Engelender, Avi Avital, Swen Hülsmann, Jackie Schiller, Herman Wolosker

Research output: Contribution to journalArticlepeer-review

Abstract

Asc-1 (SLC7A10) is an amino acid transporter whose deletion causes neurological abnormalities and early postnatal death in mice. Using metabolomics and behavioral and electrophysiological methods, we demonstrate that Asc-1 knockout mice display a marked decrease in glycine levels in the brain and spinal cord along with impairment of glycinergic inhibitory transmission, and a hyperekplexia-like phenotype that is rescued by replenishing brain glycine. Asc-1 works as a glycine and L-serine transporter, and its transport activity is required for the subsequent conversion of L-serine into glycine in vivo. Asc-1 is a novel regulator of glycine metabolism and a candidate for hyperekplexia disorders.

Original languageEnglish
Pages (from-to)590-598
Number of pages9
JournalEMBO Reports
Volume16
Issue number5
DOIs
StatePublished - 1 May 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 The Authors.

Keywords

  • D-serine
  • GlyT2
  • glycine receptor
  • hyperekplexia
  • non-ketotic hyperglycinemia

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biochemistry

Fingerprint

Dive into the research topics of 'The alanine-serine-cysteine-1 (Asc-1) transporter controls glycine levels in the brain and is required for glycinergic inhibitory transmission'. Together they form a unique fingerprint.

Cite this