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

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Item Type:	Article
Title:	Functional rescue of a defective angiotensin II AT1 receptor mutant by the Mas protooncogene
Creators Name:	Santos, E.L., Reis, R.I., Silva, R.G., Shimuta, S.U., Pecher, C., Bascands, J.L., Schanstra, J.P., Oliveira, L., Bader, M., Paiva, A.C.M., Costa-Neto, C.M. and Pesqueroa, J.B,
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.
Keywords:	Angiotensin II, AT1 receptor, Mas protooncogene, Dimerization, G-protein-coupled receptor, Animals, Cricetinae, Cricetulus
Source:	Regulatory Peptides
ISSN:	0167-0115
Publisher:	Elsevier
Volume:	141
Number:	1-3
Page Range:	159-167
Date:	7 June 2007
Official Publication:	https://doi.org/10.1016/j.regpep.2006.12.030
PubMed:	View item in PubMed

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