Characterisation of the adiponectin receptors: the non-conserved N-terminal region of AdipoR2 prevents its expression at the cell-surface.

Adiponectin is a beneficial adipokine with insulin-sensitizing, anti-inflammatory and anti-atherogenic effects. These effects are mediated by two poorly characterised, closely related, atypical seven-transmembrane receptors. In the current report we have used C-terminal, epitope-tagged AdipoR1 and AdipoR2 constructs to monitor cell-surface expression by indirect immunofluorescence microscopy and quantitative plate-based analysis.

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

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 CK2beta, 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.

Adiponectin multimerization is dependent on conserved lysines in the collagenous domain: evidence for regulation of multimerization by alterations in posttranslational modifications.

Adiponectin is a secreted, multimeric protein with insulin-sensitizing, antiatherogenic, and antiinflammatory properties. Serum adiponectin consists of trimer, hexamer, and larger high-molecular-weight (HMW) multimers, and these HMW multimers appear to be the more bioactive forms. Multimer composition of adiponectin appears to be regulated; however, the molecular mechanisms involved are unknown.