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Sci Rep. 2016 Oct 19;6:35592. doi: 10.1038/srep35592.

The astrocytic transporter SLC7A10 (Asc-1) mediates glycinergic inhibition of spinal cord motor neurons.

Author information

1
Department of Neurology, Johns Hopkins School of Medicine, 855 N. Wolfe Street, Baltimore, Maryland, 21205, USA.
2
Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland, 21205, USA.
3
Medical Scientist Training Program, Johns Hopkins School of Medicine, 1830 E. Monument Street, Baltimore, Maryland, 21205, USA.
4
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 251 Bayview Boulevard, Baltimore, Maryland, 21224, USA.
5
Brain Science Institute, Johns Hopkins School of Medicine, 855 N. Wolfe Street, Baltimore, Maryland, 21205, USA.

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.

PMID:
27759100
PMCID:
PMC5069678
DOI:
10.1038/srep35592
[Indexed for MEDLINE]
Free PMC Article

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