Characterization of relaxin receptor (RXFP1) desensitization and internalization in primary human decidual cells and RXFP1-transfected HEK293 cells.

Abstract:

:We report here the desensitization and internalization of the relaxin receptor (RXFP1) after agonist activation in both primary human decidual cells and HEK293 cells stably transfected with RXFP1. The importance of beta-arrestin 2 in these processes has also been demonstrated. Thus, in HEK-RXFP1 cells the desensitization of RXFP1 was significantly increased when beta-arrestin 2 was overexpressed. After relaxin activation, beta-arrestin 2 was translocated to the cell membrane and RXFP1 underwent rapid internalization. We have previously shown that RXFP1 forms dimers/oligomers during its biosynthesis and trafficking to the plasma membrane, we now show that internalization of RXFP1 occurs through this dimerization/oligomerization. In nonagonist stimulated cells, it is known that the majority of the RXFP1 is located intracellularly and was confirmed in the cells used here. Constitutive internalization of RXFP1 could account for this and indeed, slow but robust constitutive internalization, which was increased after agonist stimulation was demonstrated. A carboxyl-terminal deleted RXFP1 variant had a similar level of constitutive agonist-independent internalization as the wild-type RXFP1 but lost sensitivity to agonist stimulation. This demonstrated the importance of the carboxyl terminus in agonist-stimulated receptor internalization. These data suggest that the autocrine/paracrine actions of relaxin in the decidua are under additional controls at the level of expression of its receptor on the surface of its target cells.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Kern A,Bryant-Greenwood GD

doi

10.1210/en.2008-1385

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

2419-28

issue

5

eissn

0013-7227

issn

1945-7170

pii

en.2008-1385

journal_volume

150

pub_type

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