Characterization of two novel forms of the rat sulphonylurea receptor SUR1A2 and SUR1BDelta31.
1. The ATP-sensitive potassium channel (K(ATP)) of pancreatic beta-cells is composed of the sulphonylurea-binding protein, SUR1, and the inwardly rectifying K(+) channel subunit, Kir6.2. We have characterized two novel isoforms of rat SUR1 in the RINm5F insulin-secreting cell line. 2. SUR1A2 is an a...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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2002
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| _version_ | 1797053655764959232 |
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| author | Gros, L Trapp, S Dabrowski, M Ashcroft, F Bataille, D Blache, P |
| author_facet | Gros, L Trapp, S Dabrowski, M Ashcroft, F Bataille, D Blache, P |
| author_sort | Gros, L |
| collection | OXFORD |
| description | 1. The ATP-sensitive potassium channel (K(ATP)) of pancreatic beta-cells is composed of the sulphonylurea-binding protein, SUR1, and the inwardly rectifying K(+) channel subunit, Kir6.2. We have characterized two novel isoforms of rat SUR1 in the RINm5F insulin-secreting cell line. 2. SUR1A2 is an allelic variant with a single amino acid change in the first nucleotide-binding domain. Coinjection of SUR1A2 plus Kir6.2 into Xenopus oocytes or expression of a SUR1A2-Kir6.2 tandem in HEK-293 cells yielded large currents with characteristics similar to the wild-type K(ATP) channel. 3. SUR1BDelta31, detected in several human tissues, is a splice variant of the rat SUR1 gene that lacks exon 31 of the corresponding human SUR1 gene. SUR1BDelta31 lacks the TM16-TM17 transmembrane-spanning helices leading to a protein with a different transmembrane topology. Coinjection of SUR1BDelta31 plus Kir6.2 into Xenopus oocytes or expression of the Kir6.2/SUR1BDelta31 tandem construct in HEK-293 cells did not result in any current, and a surface expression assay indicated that this channel does not reach the plasma membrane. 4. SUR1A2 and SUR1A1 proteins expressed in HEK-293 cells display similar binding affinities for [(3)H]-glibenclamide, while SUR1BDelta31 shows a 500-fold lower affinity. 5. These findings confirm that TM16-TM17 of SUR1 are important for high-affinity glibenclamide binding and that their deletion impairs trafficking of the K(ATP) channel to the surface membrane. |
| first_indexed | 2024-03-06T18:46:43Z |
| format | Journal article |
| id | oxford-uuid:0ec367e3-4da4-4d3b-9bb2-69889e4e67fc |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:46:43Z |
| publishDate | 2002 |
| record_format | dspace |
| spelling | oxford-uuid:0ec367e3-4da4-4d3b-9bb2-69889e4e67fc2022-03-26T09:47:42ZCharacterization of two novel forms of the rat sulphonylurea receptor SUR1A2 and SUR1BDelta31.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0ec367e3-4da4-4d3b-9bb2-69889e4e67fcEnglishSymplectic Elements at Oxford2002Gros, LTrapp, SDabrowski, MAshcroft, FBataille, DBlache, P1. The ATP-sensitive potassium channel (K(ATP)) of pancreatic beta-cells is composed of the sulphonylurea-binding protein, SUR1, and the inwardly rectifying K(+) channel subunit, Kir6.2. We have characterized two novel isoforms of rat SUR1 in the RINm5F insulin-secreting cell line. 2. SUR1A2 is an allelic variant with a single amino acid change in the first nucleotide-binding domain. Coinjection of SUR1A2 plus Kir6.2 into Xenopus oocytes or expression of a SUR1A2-Kir6.2 tandem in HEK-293 cells yielded large currents with characteristics similar to the wild-type K(ATP) channel. 3. SUR1BDelta31, detected in several human tissues, is a splice variant of the rat SUR1 gene that lacks exon 31 of the corresponding human SUR1 gene. SUR1BDelta31 lacks the TM16-TM17 transmembrane-spanning helices leading to a protein with a different transmembrane topology. Coinjection of SUR1BDelta31 plus Kir6.2 into Xenopus oocytes or expression of the Kir6.2/SUR1BDelta31 tandem construct in HEK-293 cells did not result in any current, and a surface expression assay indicated that this channel does not reach the plasma membrane. 4. SUR1A2 and SUR1A1 proteins expressed in HEK-293 cells display similar binding affinities for [(3)H]-glibenclamide, while SUR1BDelta31 shows a 500-fold lower affinity. 5. These findings confirm that TM16-TM17 of SUR1 are important for high-affinity glibenclamide binding and that their deletion impairs trafficking of the K(ATP) channel to the surface membrane. |
| spellingShingle | Gros, L Trapp, S Dabrowski, M Ashcroft, F Bataille, D Blache, P Characterization of two novel forms of the rat sulphonylurea receptor SUR1A2 and SUR1BDelta31. |
| title | Characterization of two novel forms of the rat sulphonylurea receptor SUR1A2 and SUR1BDelta31. |
| title_full | Characterization of two novel forms of the rat sulphonylurea receptor SUR1A2 and SUR1BDelta31. |
| title_fullStr | Characterization of two novel forms of the rat sulphonylurea receptor SUR1A2 and SUR1BDelta31. |
| title_full_unstemmed | Characterization of two novel forms of the rat sulphonylurea receptor SUR1A2 and SUR1BDelta31. |
| title_short | Characterization of two novel forms of the rat sulphonylurea receptor SUR1A2 and SUR1BDelta31. |
| title_sort | characterization of two novel forms of the rat sulphonylurea receptor sur1a2 and sur1bdelta31 |
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