title: The astrocytic transporter SLC7A10 (Asc-1) mediates glycinergic inhibition of spinal cord motor neurons.
abstract: SLC7A10 (Asc-1) is a sodium-independent amino acid transporter known to facilitate transport of a number of amino acids including glycine, L-serine, L-alanine, and L-cysteine, as well as their D-enantiomers. It has been described as a neuronal transporter with a primary role related to modulation of excitatory glutamatergic neurotransmission. We find that SLC7A10 is substantially enriched in a subset of astrocytes of the caudal brain and spinal cord in a distribution corresponding with high densities of glycinergic inhibitory synapses. Accordingly, we find that spinal cord glycine levels are significantly reduced in Slc7a10-null mice and spontaneous glycinergic postsynaptic currents in motor neurons show substantially diminished amplitudes, demonstrating an essential role for SLC7A10 in glycinergic inhibitory function in the central nervous system. These observations establish the etiology of sustained myoclonus (sudden involuntary muscle movements) and early postnatal lethality characteristic of Slc7a10-null mice, and implicate SLC7A10 as a candidate gene and auto-antibody target in human hyperekplexia and stiff person syndrome, respectively.
authors.affiliation: Department of Neurology, Johns Hopkins School of Medicine, 855 N. Wolfe Street, Baltimore, Maryland, 21205, USA.|Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland, 21205, USA.|Medical Scientist Training Program, Johns Hopkins School of Medicine, 1830 E. Monument Street, Baltimore, Maryland, 21205, USA.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Ehmsen
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 251 Bayview Boulevard, Baltimore, Maryland, 21224, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 251 Bayview Boulevard, Baltimore, Maryland, 21224, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology, Johns Hopkins School of Medicine, 855 N. Wolfe Street, Baltimore, Maryland, 21205, USA.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Paladugu
authors.affiliation: Department of Neurology, Johns Hopkins School of Medicine, 855 N. Wolfe Street, Baltimore, Maryland, 21205, USA.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Johnson
authors.affiliation: Department of Neurology, Johns Hopkins School of Medicine, 855 N. Wolfe Street, Baltimore, Maryland, 21205, USA.|Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland, 21205, USA.|Brain Science Institute, Johns Hopkins School of Medicine, 855 N. Wolfe Street, Baltimore, Maryland, 21205, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Rothstein
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland, 21205, USA.
authors.forename: Sascha
authors.initials: S
authors.lastname: du Lac
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland, 21205, USA.|Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 251 Bayview Boulevard, Baltimore, Maryland, 21224, USA.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.affiliation: Department of Neurology, Johns Hopkins School of Medicine, 855 N. Wolfe Street, Baltimore, Maryland, 21205, USA.|Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland, 21205, USA.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Höke
mesh_terms: D027182:Amino Acid Transport System y+ / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D005998:Glycine / Q000378:metabolism; D006801:Humans; D000071017:Hyperekplexia / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000502:physiology*; D009207:Myoclonus / Q000235:genetics*; D013116:Spinal Cord / Q000473:pathology; D016750:Stiff-Person Syndrome / Q000235:genetics* / Q000276:immunology; D009435:Synaptic Transmission / Q000235:genetics
chemical_list: D027182:Amino Acid Transport System y+; D001324:Autoantigens; C412624:Slc7a10 protein, mouse; D005998:Glycine