Cloning, Expression, and Localization of a Rat Brain High-affinity Glycine Transporter

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1992 Aug 1

PMID 1353889

Citations 58

Authors

J Guastella

N Brecha

C Weigmann

H A Lester

N Davidson

Affiliations

Soon will be listed here.

Abstract

A cDNA clone encoding a glycine transporter has been isolated from rat brain by a combined PCR and plaque-hybridization strategy. mRNA synthesized from this clone (designated GLYT1) directs the expression of sodium- and chloride-dependent, high-affinity uptake of [3H]glycine by Xenopus oocytes. [3H]Glycine transport mediated by clone GLYT1 is blocked by sarcosine but is not blocked by methyl-aminoisobutyric acid or L-alanine, a substrate specificity similar to that described for a previously identified glycine-uptake system called system Gly. In situ hybridization reveals that GLYT1 is prominently expressed in the cervical spinal cord and brainstem, two regions of the central nervous system where glycine is a putative neurotransmitter. GLYT1 is also strongly expressed in the cerebellum and olfactory bulb and is expressed at lower levels in other brain regions. The open reading frame of the GLYT1 cDNA predicts a protein containing 633 amino acids with a molecular mass of approximately 70 kDA. The primary structure and hydropathicity profile of GLYT1 protein reveal that this protein is a member of the sodium- and chloride-dependent superfamily of transporters that utilize neurotransmitters and related substances as substrates.

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References

Usdin T, Mezey E, Chen C, Brownstein M, HOFFMAN B . Cloning of the cocaine-sensitive bovine dopamine transporter. Proc Natl Acad Sci U S A. 1991; 88(24):11168-71. PMC: 53095. DOI: 10.1073/pnas.88.24.11168. View

Glowinski J, Axelrod J . INHIBITION OF UPTAKE OF TRITIATED-NORADRENALINE IN THE INTACT RAT BRAIN BY IMIPRAMINE AND STRUCTURALLY RELATED COMPOUNDS. Nature. 1964; 204:1318-9. DOI: 10.1038/2041318a0. View

Kilty J, Lorang D, Amara S . Cloning and expression of a cocaine-sensitive rat dopamine transporter. Science. 1991; 254(5031):578-9. DOI: 10.1126/science.1948035. View

Guastella J, Nelson N, Nelson H, Czyzyk L, Keynan S, Miedel M . Cloning and expression of a rat brain GABA transporter. Science. 1990; 249(4974):1303-6. DOI: 10.1126/science.1975955. View

Horn A . Dopamine uptake: a review of progress in the last decade. Prog Neurobiol. 1990; 34(5):387-400. DOI: 10.1016/0301-0082(90)90033-d. View

Altschul S, Gish W, Miller W, Myers E, Lipman D . Basic local alignment search tool. J Mol Biol. 1990; 215(3):403-10. DOI: 10.1016/S0022-2836(05)80360-2. View

Zafra F, Gimenez C . Characteristics and adaptive regulation of glycine transport in cultured glial cells. Biochem J. 1989; 258(2):403-8. PMC: 1138376. DOI: 10.1042/bj2580403. View

Zafra F, Gimenez C . Characterization of glycine uptake in plasma membrane vesicles isolated from cultured glioblastoma cells. Brain Res. 1986; 397(1):108-16. DOI: 10.1016/0006-8993(86)91374-0. View

Ottersen O, Davanger S, Storm-Mathisen J . Glycine-like immunoreactivity in the cerebellum of rat and Senegalese baboon, Papio papio: a comparison with the distribution of GABA-like immunoreactivity and with [3H]glycine and [3H]GABA uptake. Exp Brain Res. 1987; 66(1):211-21. DOI: 10.1007/BF00236216. View

10.

Erecinska M, Troeger M, Wilson D, Silver I . The role of glial cells in regulation of neurotransmitter amino acids in the external environment. II. Mechanism of aspartate transport. Brain Res. 1986; 369(1-2):203-14. DOI: 10.1016/0006-8993(86)90529-9. View

11.

Johnston G, Iversen L . Glycine uptake in rat central nervous system slices and homogenates: evidence for different uptake systems in spinal cord and cerebral cortex. J Neurochem. 1971; 18(10):1951-61. DOI: 10.1111/j.1471-4159.1971.tb09601.x. View

12.

Wilkin G, Csillag A, Balazs R, Kingsbury A, Wilson J, Johnson A . Localization of high affinity [3H]glycine transport sites in the cerebellar cortex. Brain Res. 1981; 216(1):11-33. DOI: 10.1016/0006-8993(81)91275-0. View

13.

Halasz N, Shepherd G . Neurochemistry of the vertebrate olfactory bulb. Neuroscience. 1983; 10(3):579-619. DOI: 10.1016/0306-4522(83)90206-3. View

14.

Shimada S, Kitayama S, Lin C, Patel A, Nanthakumar E, Gregor P . Cloning and expression of a cocaine-sensitive dopamine transporter complementary DNA. Science. 1991; 254(5031):576-8. DOI: 10.1126/science.1948034. View

15.

Yamauchi A, Uchida S, Kwon H, Preston A, Robey R, Garcia-Perez A . Cloning of a Na(+)- and Cl(-)-dependent betaine transporter that is regulated by hypertonicity. J Biol Chem. 1992; 267(1):649-52. View

16.

Smith K, Borden L, Hartig P, Branchek T, Weinshank R . Cloning and expression of a glycine transporter reveal colocalization with NMDA receptors. Neuron. 1992; 8(5):927-35. DOI: 10.1016/0896-6273(92)90207-t. View

17.

Pourcho R, Goebel D, Jojich L, HAZLETT J . Immunocytochemical evidence for the involvement of glycine in sensory centers of the rat brain. Neuroscience. 1992; 46(3):643-56. DOI: 10.1016/0306-4522(92)90151-q. View

18.

Brecha N, Sternini C, Humphrey M . Cellular distribution of L-glutamate decarboxylase (GAD) and gamma-aminobutyric acidA (GABAA) receptor mRNAs in the retina. Cell Mol Neurobiol. 1991; 11(5):497-509. PMC: 11567406. DOI: 10.1007/BF00734812. View

19.

Snutch T, Leonard J, Gilbert M, Lester H, Davidson N . Rat brain expresses a heterogeneous family of calcium channels. Proc Natl Acad Sci U S A. 1990; 87(9):3391-5. PMC: 53906. DOI: 10.1073/pnas.87.9.3391. View

20.

HOFFMAN B, Mezey E, Brownstein M . Cloning of a serotonin transporter affected by antidepressants. Science. 1991; 254(5031):579-80. DOI: 10.1126/science.1948036. View