ERp46 binds to AdipoR1, but not AdipoR2, and modulates adiponectin signalling

Charlton, HK, Webster, J, Kruger, S, Simpson, F, Richards, AA and Whitehead, JP (2010) ERp46 binds to AdipoR1, but not AdipoR2, and modulates adiponectin signalling. Biochemical and Biophysical Research Communications, 392 2: 234-239. doi:10.1016/j.bbrc.2010.01.029

Author Charlton, HK
Webster, J
Kruger, S
Simpson, F
Richards, AA
Whitehead, JP
Title ERp46 binds to AdipoR1, but not AdipoR2, and modulates adiponectin signalling
Journal name Biochemical and Biophysical Research Communications   Check publisher's open access policy
ISSN 0006-291X
Publication date 2010-02-05
Sub-type Article (original research)
DOI 10.1016/j.bbrc.2010.01.029
Volume 392
Issue 2
Start page 234
End page 239
Total pages 6
Place of publication Maryland Heights, MO, United States
Publisher Academic Press
Collection year 2011
Language eng
Abstract The pleiotropic effects of the insulin-sensitizing adipokine adiponectin are mediated, at least in part, by two seven-transmembrane domain receptors AdipoR1 and AdipoR2. Recent reports indicate a role for AdipoR-binding proteins, namely APPL1, RACK1 and CK2β, in proximal signal transduction events. Here we demonstrate that endoplasmic reticulum protein 46 (ERp46) interacts specifically with AdipoR1 and provide evidence that ERp46 modulates adiponectin signalling. Co-immunoprecipitation followed by mass spectrometry identified ERp46 as an AdipoR1-, but not AdipoR2-, interacting protein. Analysis of truncated constructs and GST-fusion proteins revealed the interaction was mediated by the cytoplasmic, N-terminal residues (1-70) of AdipoR1. Indirect immunofluorescence microscopy and subcellular fractionation studies demonstrated that ERp46 was present in the ER and the plasma membrane (PM). Transient knockdown of ERp46 increased the levels of AdipoR1, and AdipoR2, at the PM and this correlated with increased adiponectin-stimulated phosphorylation of AMPK. In contrast, adiponectin-stimulated phosphorylation of p38MAPK was reduced following ERp46 knockdown. Collectively these results establish ERp46 as the first AdipoR1-specific interacting protein and suggest a role for ERp46 in adiponectin receptor biology and adiponectin signalling. © 2010 Elsevier Inc. All rights reserved.
Keyword Adiponectin
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
UQ Diamantina Institute Publications
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Created: Sun, 07 Mar 2010, 00:07:53 EST