The alanine-serine-cysteine-1 (Asc-1) transporter controls glycine levels in the brain and is required for glycinergic inhibitory transmission |
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| Authors: | Hazem Safory Samah Neame Yoav Shulman Salman Zubedat Inna Radzishevsky Dina Rosenberg Hagit Sason Simone Engelender Avi Avital Swen Hülsmann Jackie Schiller Herman Wolosker |
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| Institution: | 1The Rappaport Faculty of Medicine and Research Institute, Technion–Israel Institute of Technology, Haifa, Israel;2Emek Medical Center, Afula, Israel;3Department of Anesthesiology, Emergency and Intensive Care Medicine and Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Georg-August-University, Göttingen, Germany |
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| 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. |
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| Keywords: | glycine receptor GlyT2 hyperekplexia non-ketotic hyperglycinemia D-serine |
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