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G-protein-coupled receptor 30 interacts with receptor activity-modifying protein 3 and confers sex-dependent cardioprotection

Lenhart, P.M. ; Broselid, Stefan LU ; Barrick, C.J. ; Leeb-Lundberg, Fredrik LU and Hellsten Caron, Murielle LU (2013) In Journal of Molecular Endocrinology 51(1). p.191-202
Abstract
Abstract

Receptor activity-modifying protein 3 (RAMP3) is a single-pass transmembrane protein known to interact with and affect the trafficking of several G-protein-coupled receptors (GPCRs). We sought to determine whether RAMP3 interacts with GPR30, also known as G-protein-coupled estrogen receptor 1. GPR30 is a GPCR that binds estradiol and has important roles in cardiovascular and endocrine physiology. Using bioluminescence resonance energy transfer titration studies, co-immunoprecipitation, and confocal microscopy, we show that GPR30 and RAMP3 interact. Furthermore, the presence of GPR30 leads to increased expression of RAMP3 at the plasma membrane in HEK293 cells. In vivo, there are marked sex differences in the subcellular... (More)
Abstract

Receptor activity-modifying protein 3 (RAMP3) is a single-pass transmembrane protein known to interact with and affect the trafficking of several G-protein-coupled receptors (GPCRs). We sought to determine whether RAMP3 interacts with GPR30, also known as G-protein-coupled estrogen receptor 1. GPR30 is a GPCR that binds estradiol and has important roles in cardiovascular and endocrine physiology. Using bioluminescence resonance energy transfer titration studies, co-immunoprecipitation, and confocal microscopy, we show that GPR30 and RAMP3 interact. Furthermore, the presence of GPR30 leads to increased expression of RAMP3 at the plasma membrane in HEK293 cells. In vivo, there are marked sex differences in the subcellular localization of GPR30 in cardiac cells, and the hearts of Ramp3(-/-) mice also show signs of GPR30 mislocalization. To determine whether this interaction might play a role in cardiovascular disease, we treated Ramp3(+)(/)(+) and Ramp3(-/-) mice on a heart disease-prone genetic background with G-1, a specific agonist for GPR30. Importantly, this in vivo activation of GPR30 resulted in a significant reduction in cardiac hypertrophy and perivascular fibrosis that is both RAMP3 and sex dependent. Our results demonstrate that GPR30-RAMP3 interaction has functional consequences on the localization of these proteins both in vitro and in vivo and that RAMP3 is required for GPR30-mediated cardioprotection. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
G-protein-coupled receptors, cardiac hypertrophy, cardioprotection, estradiol
in
Journal of Molecular Endocrinology
volume
51
issue
1
pages
191 - 202
publisher
Society for Endocrinology
external identifiers
  • wos:000322708900019
  • scopus:84879985064
  • pmid:23674134
ISSN
1479-6813
DOI
10.1530/JME-13-0021
language
English
LU publication?
yes
id
40a95cec-fa9b-4afa-8701-e1fbab490905 (old id 3972702)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23674134
date added to LUP
2016-04-01 13:37:01
date last changed
2022-02-11 22:04:29
@article{40a95cec-fa9b-4afa-8701-e1fbab490905,
  abstract     = {{Abstract<br/><br>
Receptor activity-modifying protein 3 (RAMP3) is a single-pass transmembrane protein known to interact with and affect the trafficking of several G-protein-coupled receptors (GPCRs). We sought to determine whether RAMP3 interacts with GPR30, also known as G-protein-coupled estrogen receptor 1. GPR30 is a GPCR that binds estradiol and has important roles in cardiovascular and endocrine physiology. Using bioluminescence resonance energy transfer titration studies, co-immunoprecipitation, and confocal microscopy, we show that GPR30 and RAMP3 interact. Furthermore, the presence of GPR30 leads to increased expression of RAMP3 at the plasma membrane in HEK293 cells. In vivo, there are marked sex differences in the subcellular localization of GPR30 in cardiac cells, and the hearts of Ramp3(-/-) mice also show signs of GPR30 mislocalization. To determine whether this interaction might play a role in cardiovascular disease, we treated Ramp3(+)(/)(+) and Ramp3(-/-) mice on a heart disease-prone genetic background with G-1, a specific agonist for GPR30. Importantly, this in vivo activation of GPR30 resulted in a significant reduction in cardiac hypertrophy and perivascular fibrosis that is both RAMP3 and sex dependent. Our results demonstrate that GPR30-RAMP3 interaction has functional consequences on the localization of these proteins both in vitro and in vivo and that RAMP3 is required for GPR30-mediated cardioprotection.}},
  author       = {{Lenhart, P.M. and Broselid, Stefan and Barrick, C.J. and Leeb-Lundberg, Fredrik and Hellsten Caron, Murielle}},
  issn         = {{1479-6813}},
  keywords     = {{G-protein-coupled receptors; cardiac hypertrophy; cardioprotection; estradiol}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{191--202}},
  publisher    = {{Society for Endocrinology}},
  series       = {{Journal of Molecular Endocrinology}},
  title        = {{G-protein-coupled receptor 30 interacts with receptor activity-modifying protein 3 and confers sex-dependent cardioprotection}},
  url          = {{http://dx.doi.org/10.1530/JME-13-0021}},
  doi          = {{10.1530/JME-13-0021}},
  volume       = {{51}},
  year         = {{2013}},
}