Ivermectin and Nodulisporic Acid Receptors in Drosophila melanogaster Contain Both -Aminobutyric Acid-Gated Rdl and Glutamate
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- 作者：Steven W. Ludmerer ; Vivien A. Warren ; Brande S. Williams ; Yingcong Zheng ; David C. Hunt ; Michelle B. Ayer ; Michael A. Wallace ; Ashok G. Chaudhary ; Marjorie A. Egan ; Peter T. Meinke ; Dennis C. Dean ; Ma
- 刊名：Biochemistry
- 出版年：2002
- 出版时间：May 21, 2002
- 年：2002
- 卷：41
- 期：20
- 页码：6548 - 6560
- 全文大小：175K
- 年卷期：v.41,no.20(May 21, 2002)
- ISSN：1520-4995
文摘
35S-labeled derivatives of the insecticides nodulisporic acid and ivermectin were synthesizedand demonstrated to bind with high affinity to a population of receptors in Drosophila head membranesthat were previously shown to be associated with a glutamate-gated chloride channel. Nodulisporic acidbinding was modeled as binding to a single population of receptors. Ivermectin binding was composed ofat least two kinetically distinct receptor populations, only one of which was associated with nodulisporicacid binding. The binding of these two ligands was modulated by glutamate, ivermectin, and antagonistsof invertebrate 
-aminobutyric acid (GABA)ergic receptors. Because solubilized nodulisporic acid andivermectin receptors comigrated as 230-kDa complexes by gel filtration, antisera specific for both theDrosophila glutamate-gated chloride channel subunit GluCl
(DmGluCl) and the GABA-gated chloridechannel subunit Rdl (DmRdl) proteins were generated and used to examine the possible coassembly ofthese two subunits within a single receptor complex. DmGluCl antibodies immunoprecipitated all of theivermectin and nodulisporic acid receptors solubilized by detergent from Drosophila head membranes.DmRdl antibodies also immunoprecipitated all solubilized nodulisporic receptors, but only ~70% of theivermectin receptors. These data suggest that both DmGluCl and DmRdl are components of nodulisporicacid and ivermectin receptors, and that there also exists a distinct class of ivermectin receptors that containsthe DmGluCl subunit but not the DmRdl subunit. This co-association of DmGluCl and DmRdl representsthe first biochemical and immunological evidence of coassembly of subunits from two different subclassesof ligand-gated ion channel subunits.
-aminobutyric acid (GABA)ergic receptors. Because solubilized nodulisporic acid andivermectin receptors comigrated as 230-kDa complexes by gel filtration, antisera specific for both theDrosophila glutamate-gated chloride channel subunit GluCl (DmGluCl) and the GABA-gated chloridechannel subunit Rdl (DmRdl) proteins were generated and used to examine the possible coassembly ofthese two subunits within a single receptor complex. DmGluCl antibodies immunoprecipitated all of theivermectin and nodulisporic acid receptors solubilized by detergent from Drosophila head membranes.DmRdl antibodies also immunoprecipitated all solubilized nodulisporic receptors, but only ~70% of theivermectin receptors. These data suggest that both DmGluCl and DmRdl are components of nodulisporicacid and ivermectin receptors, and that there also exists a distinct class of ivermectin receptors that containsthe DmGluCl subunit but not the DmRdl subunit. This co-association of DmGluCl and DmRdl representsthe first biochemical and immunological evidence of coassembly of subunits from two different subclassesof ligand-gated ion channel subunits.