Dominant negative effects of human follicle-stimulating hormone receptor expression-deficient mutants on wild-type receptor cell surface expression. Rescue of oligomerization-dependent defective receptor expression by using cognate decoys
| Autor: | Alfredo Ulloa-Aguirre, Teresa Zariñán, James A. Dias, Patricia Casas-González, P. Michael Conn, Marco Allán Pérez-Solis, Guadalupe Maya-Núñez |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Protein Folding
endocrine system Dominant Negative Receptor Receptor expression Blotting Western Molecular Sequence Data Receptors Cell Surface Biology Biochemistry Article Cell Line Thyrotropin receptor Endocrinology Enzyme-linked receptor Humans Amino Acid Sequence Receptor Molecular Biology luteinizing hormone/choriogonadotropin receptor Molecular biology Gene Expression Regulation Hormone receptor Mutation Receptors FSH Electrophoresis Polyacrylamide Gel Follicle-stimulating hormone receptor Dimerization |
| Zdroj: | Molecular and Cellular Endocrinology. 321:112-122 |
| ISSN: | 0303-7207 |
| Popis: | Current evidence indicates that G protein-coupled receptors form dimers that may affect biogenesis and membrane targeting of the complexed receptors. We here analyzed whether expression-deficient follicle-stimulating hormone receptor (FSHR) mutants exert dominant negative actions on wild-type FSHR cell surface membrane expression. Co-transfection of constant amounts of wild-type receptor cDNA and increasing quantities of mutant (R556A or R618A) FSHR cDNAs progressively decreased agonist-stimulated cAMP accumulation, [(125)I]-FSH binding, and plasma membrane expression of the mature wild-type FSHR species. Co-transfection of wild-type FSHR fragments involving transmembrane domains 5-6, or transmembrane domain 7 and/or the carboxyl-terminus specifically rescued wild-type FSHR expression from the transdominant inhibition by the mutants. Mutant FSHRs also inhibited function of the luteinizing hormone receptor but not that of the thyrotropin receptor or non-related receptors. Defective intracellular transport and/or interference with proper maturation due to formation of misfolded mutant:wild-type receptor complexes may explain the negative effects provoked by the altered FSHRs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect