Abstract
A 3.7-kb cDNA fragment, designated rat-XT1, was isolated from a rat whole-brain cDNA library. The nucleotide sequence of XT1 codes for a 727 amino acid protein with a calculated molecular mass of 81,139 Da and 12 putative transmembrane domains. This protein shares significant homology (28-32%) with the monoamine- (dopamine, norepinephrine, serotonin), amino acid- (taurine, proline, GABA, glycine), choline-, and betaine-, Na+/Cl--dependent transporters. The homology is especially high within the first, second, sixth, and eighth transmembrane domains (45-75%). Thus, XT1 clearly belongs to the Na+/Cl--dependent neurotransmitter transporter superfamily. However, XT1 may define a new subfamily of transporter because it differs structurally from other members of this family in that the extracellular loop linking transmembrane domains 7 and 8 and the C-terminal tail are significantly larger in size. Transient or stable expression of rat-XT1 failed to confer to the transfected cells the ability to transport actively any of the >60 established or putative neurotransmitter substances assessed. Northern blot analyses of peripheral and neural tissues demonstrated that expression of the 8-kb XT1 mRNA is essentially restricted to the nervous system. In situ hybridization demonstrated a broad but discrete localization of XT1 message in the CNS, particularly in the cerebellum (Purkinje and granular cell layers), the hippocampus (pyramidal and granular cell layers), and the thalamus and throughout the cerebral cortex. This distribution parallels that of the neurotransmitters glutamate and aspartate; however, neither of these excitatory amino acids is a substrate for transport. One noticeable exception to the codistribution of the mRNA for rat-XT1 and these excitatory neurotransmitters is the cerebellar Purkinje cell layer, in which GABAergic neurons are localized. The gene encoding for XT1 is localized to the mouse chromosome 3 in the vicinity of the locus for the mouse neurological disorder spastic (spa).
| Original language | English (US) |
|---|---|
| Pages (from-to) | 445-455 |
| Number of pages | 11 |
| Journal | Journal of Neurochemistry |
| Volume | 62 |
| Issue number | 2 |
| State | Published - Feb 1994 |
| Externally published | Yes |
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Keywords
- CNS
- GABA
- Glutamate/aspartate
- In situ hybridization
- Molecular cloning
- Na/Cl-dependent neurotransmitter transporter
- Spastic mouse
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience
Cite this
Characterization of an atypical member of the Na+/Cl--dependent transporter family : Chromosomal localization and distribution in GABAergic and glutamatergic neurons in the rat brain. / El Mestikawy, Salah; Giros, Bruno; Pohl, Michel; Hamon, Michel; Kingsmore, Stephen F.; Seldin, Michael F; Caron, Marc G.
In: Journal of Neurochemistry, Vol. 62, No. 2, 02.1994, p. 445-455.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Characterization of an atypical member of the Na+/Cl--dependent transporter family
T2 - Chromosomal localization and distribution in GABAergic and glutamatergic neurons in the rat brain
AU - El Mestikawy, Salah
AU - Giros, Bruno
AU - Pohl, Michel
AU - Hamon, Michel
AU - Kingsmore, Stephen F.
AU - Seldin, Michael F
AU - Caron, Marc G.
PY - 1994/2
Y1 - 1994/2
N2 - A 3.7-kb cDNA fragment, designated rat-XT1, was isolated from a rat whole-brain cDNA library. The nucleotide sequence of XT1 codes for a 727 amino acid protein with a calculated molecular mass of 81,139 Da and 12 putative transmembrane domains. This protein shares significant homology (28-32%) with the monoamine- (dopamine, norepinephrine, serotonin), amino acid- (taurine, proline, GABA, glycine), choline-, and betaine-, Na+/Cl--dependent transporters. The homology is especially high within the first, second, sixth, and eighth transmembrane domains (45-75%). Thus, XT1 clearly belongs to the Na+/Cl--dependent neurotransmitter transporter superfamily. However, XT1 may define a new subfamily of transporter because it differs structurally from other members of this family in that the extracellular loop linking transmembrane domains 7 and 8 and the C-terminal tail are significantly larger in size. Transient or stable expression of rat-XT1 failed to confer to the transfected cells the ability to transport actively any of the >60 established or putative neurotransmitter substances assessed. Northern blot analyses of peripheral and neural tissues demonstrated that expression of the 8-kb XT1 mRNA is essentially restricted to the nervous system. In situ hybridization demonstrated a broad but discrete localization of XT1 message in the CNS, particularly in the cerebellum (Purkinje and granular cell layers), the hippocampus (pyramidal and granular cell layers), and the thalamus and throughout the cerebral cortex. This distribution parallels that of the neurotransmitters glutamate and aspartate; however, neither of these excitatory amino acids is a substrate for transport. One noticeable exception to the codistribution of the mRNA for rat-XT1 and these excitatory neurotransmitters is the cerebellar Purkinje cell layer, in which GABAergic neurons are localized. The gene encoding for XT1 is localized to the mouse chromosome 3 in the vicinity of the locus for the mouse neurological disorder spastic (spa).
AB - A 3.7-kb cDNA fragment, designated rat-XT1, was isolated from a rat whole-brain cDNA library. The nucleotide sequence of XT1 codes for a 727 amino acid protein with a calculated molecular mass of 81,139 Da and 12 putative transmembrane domains. This protein shares significant homology (28-32%) with the monoamine- (dopamine, norepinephrine, serotonin), amino acid- (taurine, proline, GABA, glycine), choline-, and betaine-, Na+/Cl--dependent transporters. The homology is especially high within the first, second, sixth, and eighth transmembrane domains (45-75%). Thus, XT1 clearly belongs to the Na+/Cl--dependent neurotransmitter transporter superfamily. However, XT1 may define a new subfamily of transporter because it differs structurally from other members of this family in that the extracellular loop linking transmembrane domains 7 and 8 and the C-terminal tail are significantly larger in size. Transient or stable expression of rat-XT1 failed to confer to the transfected cells the ability to transport actively any of the >60 established or putative neurotransmitter substances assessed. Northern blot analyses of peripheral and neural tissues demonstrated that expression of the 8-kb XT1 mRNA is essentially restricted to the nervous system. In situ hybridization demonstrated a broad but discrete localization of XT1 message in the CNS, particularly in the cerebellum (Purkinje and granular cell layers), the hippocampus (pyramidal and granular cell layers), and the thalamus and throughout the cerebral cortex. This distribution parallels that of the neurotransmitters glutamate and aspartate; however, neither of these excitatory amino acids is a substrate for transport. One noticeable exception to the codistribution of the mRNA for rat-XT1 and these excitatory neurotransmitters is the cerebellar Purkinje cell layer, in which GABAergic neurons are localized. The gene encoding for XT1 is localized to the mouse chromosome 3 in the vicinity of the locus for the mouse neurological disorder spastic (spa).
KW - CNS
KW - GABA
KW - Glutamate/aspartate
KW - In situ hybridization
KW - Molecular cloning
KW - Na/Cl-dependent neurotransmitter transporter
KW - Spastic mouse
UR - http://www.scopus.com/inward/record.url?scp=0028006216&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028006216&partnerID=8YFLogxK
M3 - Article
C2 - 8294906
AN - SCOPUS:0028006216
VL - 62
SP - 445
EP - 455
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 2
ER -