title: Characterisation of the adiponectin receptors: Differential cell-surface expression and temporal signalling profiles of AdipoR1 and AdipoR2 are regulated by the non-conserved N-terminal trunks.
abstract: The adiponectin axis regulates cardiometabolic and inflammatory tone making it an attractive therapeutic focus. Rudimentary understanding of the adiponectin receptors, AdipoR1 and AdipoR2, constrains our ability to target these atypical seven trans-membrane proteins. Here, we aimed to further elaborate the molecular details governing cell-surface expression and signal transduction by transient expression of AdipoR1 or AdipoR2 in HEK293 cells. Following serum starvation, adiponectin reduced cell-surface expression of both receptors, consistent with internalisation, and promoted phosphorylation of downstream effectors. Temporal phosphorylation profiles differed with AdipoR1 and AdipoR2 transduced signals peaking at 15 min and 24 h. Analysis of receptor chimeras showed that the non-conserved N-terminal trunks (AdipoR1(1-70) and AdipoR2(1-81)) define the temporal signalling profiles and contain multiple regions that promote or inhibit cell-surface expression, respectively. These findings highlight the importance of the non-conserved N-terminal trunks and demonstrate that cell-surface expression of AdipoR1 and AdipoR2 is required for effective coupling to downstream effectors.
authors.affiliation: Translational Research Institute, Mater Research Institute, University of Queensland, Brisbane, QLD, Australia.
authors.forename: Sahar
authors.initials: S
authors.lastname: Keshvari
authors.affiliation: Translational Research Institute, Mater Research Institute, University of Queensland, Brisbane, QLD, Australia. Electronic address: jon.whitehead@mater.uq.edu.au.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Whitehead
mesh_terms: D000818:Animals; D016466:CHO Cells; D018929:Cell Culture Techniques; D002462:Cell Membrane / Q000378:metabolism*; D003412:Cricetulus; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D054419:Receptors, Adiponectin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D054419:Receptors, Adiponectin
keywords: Adiponectin; Receptor; Signal transduction