title: The alanine-serine-cysteine-1 (Asc-1) transporter controls glycine levels in the brain and is required for glycinergic inhibitory transmission.
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.
authors.affiliation: The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Hazem
authors.initials: H
authors.lastname: Safory
authors.affiliation: The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Samah
authors.initials: S
authors.lastname: Neame
authors.affiliation: The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Shulman
authors.affiliation: The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Salman
authors.initials: S
authors.lastname: Zubedat
authors.affiliation: The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Inna
authors.initials: I
authors.lastname: Radzishevsky
authors.affiliation: The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Dina
authors.initials: D
authors.lastname: Rosenberg
authors.affiliation: The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Hagit
authors.initials: H
authors.lastname: Sason
authors.affiliation: The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Simone
authors.initials: S
authors.lastname: Engelender
authors.affiliation: The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel Emek Medical Center, Afula, Israel.
authors.forename: Avi
authors.initials: A
authors.lastname: Avital
authors.affiliation: Department of Anesthesiology, Emergency and Intensive Care Medicine and Center for Nanoscale Microscopy and Molecular Physiology of the Brain Georg-August-University, Göttingen, Germany.
authors.forename: Swen
authors.initials: S
authors.lastname: Hülsmann
authors.affiliation: The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Jackie
authors.initials: J
authors.lastname: Schiller
authors.affiliation: The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel hwolosker@tx.technion.ac.il.
authors.forename: Herman
authors.initials: H
authors.lastname: Wolosker
mesh_terms: D027182:Amino Acid Transport System y+ / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D005838:Genotype; D005998:Glycine / Q000378:metabolism*; D007002:Hypoglossal Nerve / Q000166:cytology; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D018009:Receptors, Glycine / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics
chemical_list: D027182:Amino Acid Transport System y+; D018009:Receptors, Glycine; C412624:Slc7a10 protein, mouse; D012694:Serine; D005998:Glycine
keywords: D‐serine; GlyT2; glycine receptor; hyperekplexia; non‐ketotic hyperglycinemia