Abstract
The ρ1 γ-aminobutyrate receptor (GABA(ρ1)) is expressed predominantly in the retina and forms homomeric GABA-gated Cl- channels that are clearly different from the multisubunit GABA(A) receptors. In contrast to these, GAB(ρ1) receptors desensitize very little and are not blocked by bicuculline. In addition to GAB(ρ1), two new variants were identified in human retina cDNA libraries. Cloning and sequence analysis showed that both variants contain large deletions in the putative extracellular domain of the receptor. These deletions extend from a common 5' site to different 3' sites. The cDNA with the largest deletion, named GABA(ρ)Δ450, contains a complete ORF identical to that of GABA(ρ1) but missing 450 nt. This cDNA encodes a protein of 323 aa, identical to the GABA(ρ1), but has a deletion of 150 aa in the amino-terminal extracellular domain. GABA(ρ1)Δ450 mRNA injected into Xenopus oocytes did not produce functional GABA receptors. The second GABA(ρ1) variant (GABA(ρ1)Δ51) contains a 51-nt deletion. In Xenopus oocytes, GABA(ρ1)Δ51 led to the expression of GABA receptors that had the essential GABAρ1 characteristics of low desensitization and bicuculline resistance. Therefore, alternative splicing increases the coding potential of this gene family expressed in the human retina, but the functional diversity created by the alternative spliced forms is still not understood.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4019-4022 |
| Number of pages | 4 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 95 |
| Issue number | 7 |
| DOIs | |
| State | Published - Mar 31 1998 |
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ASJC Scopus subject areas
- Genetics
- General
Cite this
Cloning and functional expression of alternative spliced variants of the ρ1 γ-aminobutyrate receptor. / Martínez-Torres, Ataúlfo; Vazquez, Ana E.; Panicker, Mitradas M.; Miledi, Ricardo.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 7, 31.03.1998, p. 4019-4022.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cloning and functional expression of alternative spliced variants of the ρ1 γ-aminobutyrate receptor
AU - Martínez-Torres, Ataúlfo
AU - Vazquez, Ana E.
AU - Panicker, Mitradas M.
AU - Miledi, Ricardo
PY - 1998/3/31
Y1 - 1998/3/31
N2 - The ρ1 γ-aminobutyrate receptor (GABA(ρ1)) is expressed predominantly in the retina and forms homomeric GABA-gated Cl- channels that are clearly different from the multisubunit GABA(A) receptors. In contrast to these, GAB(ρ1) receptors desensitize very little and are not blocked by bicuculline. In addition to GAB(ρ1), two new variants were identified in human retina cDNA libraries. Cloning and sequence analysis showed that both variants contain large deletions in the putative extracellular domain of the receptor. These deletions extend from a common 5' site to different 3' sites. The cDNA with the largest deletion, named GABA(ρ)Δ450, contains a complete ORF identical to that of GABA(ρ1) but missing 450 nt. This cDNA encodes a protein of 323 aa, identical to the GABA(ρ1), but has a deletion of 150 aa in the amino-terminal extracellular domain. GABA(ρ1)Δ450 mRNA injected into Xenopus oocytes did not produce functional GABA receptors. The second GABA(ρ1) variant (GABA(ρ1)Δ51) contains a 51-nt deletion. In Xenopus oocytes, GABA(ρ1)Δ51 led to the expression of GABA receptors that had the essential GABAρ1 characteristics of low desensitization and bicuculline resistance. Therefore, alternative splicing increases the coding potential of this gene family expressed in the human retina, but the functional diversity created by the alternative spliced forms is still not understood.
AB - The ρ1 γ-aminobutyrate receptor (GABA(ρ1)) is expressed predominantly in the retina and forms homomeric GABA-gated Cl- channels that are clearly different from the multisubunit GABA(A) receptors. In contrast to these, GAB(ρ1) receptors desensitize very little and are not blocked by bicuculline. In addition to GAB(ρ1), two new variants were identified in human retina cDNA libraries. Cloning and sequence analysis showed that both variants contain large deletions in the putative extracellular domain of the receptor. These deletions extend from a common 5' site to different 3' sites. The cDNA with the largest deletion, named GABA(ρ)Δ450, contains a complete ORF identical to that of GABA(ρ1) but missing 450 nt. This cDNA encodes a protein of 323 aa, identical to the GABA(ρ1), but has a deletion of 150 aa in the amino-terminal extracellular domain. GABA(ρ1)Δ450 mRNA injected into Xenopus oocytes did not produce functional GABA receptors. The second GABA(ρ1) variant (GABA(ρ1)Δ51) contains a 51-nt deletion. In Xenopus oocytes, GABA(ρ1)Δ51 led to the expression of GABA receptors that had the essential GABAρ1 characteristics of low desensitization and bicuculline resistance. Therefore, alternative splicing increases the coding potential of this gene family expressed in the human retina, but the functional diversity created by the alternative spliced forms is still not understood.
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UR - http://www.scopus.com/inward/citedby.url?scp=0032584229&partnerID=8YFLogxK
U2 - 10.1073/pnas.95.7.4019
DO - 10.1073/pnas.95.7.4019
M3 - Article
C2 - 9520485
AN - SCOPUS:0032584229
VL - 95
SP - 4019
EP - 4022
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 7
ER -