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

doi:10.15252/embr.201439561

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 journal › Article › peer-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 language	English
Pages (from-to)	590-598
Number of pages	9
Journal	EMBO Reports
Volume	16
Issue number	5
DOIs	https://doi.org/10.15252/embr.201439561
State	Published - 1 May 2015
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2015 The Authors.

Keywords

D-serine
GlyT2
glycine receptor
hyperekplexia
non-ketotic hyperglycinemia

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.15252/embr.201439561

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Safory, H., Neame, S., Shulman, Y., Zubedat, S., Radzishevsky, I., Rosenberg, D., Sason, H., Engelender, S., Avital, A., Hülsmann, S., Schiller, J., & Wolosker, H. (2015). The alanine-serine-cysteine-1 (Asc-1) transporter controls glycine levels in the brain and is required for glycinergic inhibitory transmission. EMBO Reports, 16(5), 590-598. https://doi.org/10.15252/embr.201439561

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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.",

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author = "Hazem Safory and Samah Neame and Yoav Shulman and Salman Zubedat and Inna Radzishevsky and Dina Rosenberg and Hagit Sason and Simone Engelender and Avi Avital and Swen H{\"u}lsmann and Jackie Schiller and Herman Wolosker",

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doi = "10.15252/embr.201439561",

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Safory, H, Neame, S, Shulman, Y, Zubedat, S, Radzishevsky, I, Rosenberg, D, Sason, H, Engelender, S, Avital, A, Hülsmann, S, Schiller, J & Wolosker, H 2015, 'The alanine-serine-cysteine-1 (Asc-1) transporter controls glycine levels in the brain and is required for glycinergic inhibitory transmission', EMBO Reports, vol. 16, no. 5, pp. 590-598. https://doi.org/10.15252/embr.201439561

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T1 - The alanine-serine-cysteine-1 (Asc-1) transporter controls glycine levels in the brain and is required for glycinergic inhibitory transmission

AU - Safory, Hazem

AU - Neame, Samah

AU - Shulman, Yoav

AU - Zubedat, Salman

AU - Radzishevsky, Inna

AU - Rosenberg, Dina

AU - Sason, Hagit

AU - Engelender, Simone

AU - Avital, Avi

AU - Hülsmann, Swen

AU - Schiller, Jackie

AU - Wolosker, Herman

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

KW - D-serine

KW - GlyT2

KW - glycine receptor

KW - hyperekplexia

KW - non-ketotic hyperglycinemia

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DO - 10.15252/embr.201439561

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AN - SCOPUS:84928926220

SN - 1469-221X

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JO - EMBO Reports

JF - EMBO Reports

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ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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