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Functional rescue of a defective angiotensin II AT1 receptor mutant by the Mas protooncogene.

Abstract : Earlier studies with Mas protooncogene, a member of the G-protein-coupled receptor family, have proposed this gene to code for a functional AngII receptor, however further results did not confirm this assumption. In this work we investigated the hypothesis that a heterodimeration AT(1)/Mas could result in a functional interaction between both receptors. For this purpose, CHO or COS-7 cells were transfected with the wild-type AT(1) receptor, a non-functional AT(1) receptor double mutant (C18F-K20A) and Mas or with WT/Mas and C18F-K20A/Mas. Cells single-expressing Mas or C18F/K20A did not show any binding for AngII. The co-expression of the wild-type AT(1) receptor and Mas showed a binding profile similar to that observed for the wild-type AT(1) expressed alone. Surprisingly, the co-expression of the double mutant C18F/K20A and Mas evoked a total recovery of the binding affinity for AngII to a level similar to that obtained for the wild-type AT(1). Functional measurements using inositol phosphate and extracellular acidification rate assays also showed a clear recovery of activity for AngII on cells co-expressing the mutant C18F/K20A and Mas. In addition, immunofluorescence analysis localized the AT(1) receptor mainly at the plasma membrane and the mutant C18F-K20A exclusively inside the cells. However, the co-expression of C18F-K20A mutant with the Mas changed the distribution pattern of the mutant, with intense signals at the plasma membrane, comparable to those observed in cells expressing the wild-type AT(1) receptor. These results support the hypothesis that Mas is able to rescue binding and functionality of the defective C18F-K20A mutant by dimerization.
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https://www.hal.inserm.fr/inserm-00409777
Contributor : Marie Francoise Simon <>
Submitted on : Wednesday, August 12, 2009 - 4:18:44 PM
Last modification on : Friday, July 24, 2020 - 9:56:06 AM

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Edson Santos, Rosana Reis, Ronaldo Silva, Suma Shimuta, Christiane Pecher, et al.. Functional rescue of a defective angiotensin II AT1 receptor mutant by the Mas protooncogene.. Regulatory Peptides, Elsevier, 2007, 141 (1-3), pp.159-67. ⟨10.1016/j.regpep.2006.12.030⟩. ⟨inserm-00409777⟩

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