TY - JOUR
T1 - Pattern of intra-family hetero-oligomerization involving the G-protein-coupled secretin receptor
AU - Harikumar, Kaleeckal G.
AU - Morfis, Maria M.
AU - Sexton, Patrick M.
AU - Miller, Laurence J.
N1 - Funding Information:
Acknowledgments The authors thank Ms. L.-A. Bruins for excellent technical assistance and Ms. E. Posthumus for secretarial assistance. This work was supported by grants from the National Institutes of Health, DK46577 (LJM), National Health and Medical Research Council of Australia (NHMRC) grant 436780 (PMS), and by the Fiterman Foundation (LJM). PMS is a NHMRC Principal Research Fellow.
PY - 2008/11
Y1 - 2008/11
N2 - Oligomerization of G-protein-coupled receptors (GPCRs) is emerging as a mechanism for regulation and functional modification, although it has been studied most extensively for Family A receptors. Family B receptors have clear structural differences from Family A. In this paper, we have systematically evaluated GPCRs that are capable of association with the prototypic Family B secretin receptor. All of the receptor constructs were shown to traffic normally to the plasma membrane. We utilized receptor bioluminescence resonance energy transfer (BRET) to determine the presence of constitutive and ligand-dependent receptor association. Extensive intra-family and no cross-family association was observed. Of the nine Family B receptors studied, all constitutively yielded a significant BRET signal with the secretin receptor, except for the calcitonin receptor. Each of the associating hetero-oligomeric receptor pairs generated a BRET signal of similar intensity, less than that of homo-oligomeric secretin receptors. BRET signals from some receptor pairs were reduced by ligand occupation, but none were increased by this treatment. Thus, Family B GPCR oligomerization occurs, with many structurally related members associating with each other. The specific functional implications of this need to be further evaluated.
AB - Oligomerization of G-protein-coupled receptors (GPCRs) is emerging as a mechanism for regulation and functional modification, although it has been studied most extensively for Family A receptors. Family B receptors have clear structural differences from Family A. In this paper, we have systematically evaluated GPCRs that are capable of association with the prototypic Family B secretin receptor. All of the receptor constructs were shown to traffic normally to the plasma membrane. We utilized receptor bioluminescence resonance energy transfer (BRET) to determine the presence of constitutive and ligand-dependent receptor association. Extensive intra-family and no cross-family association was observed. Of the nine Family B receptors studied, all constitutively yielded a significant BRET signal with the secretin receptor, except for the calcitonin receptor. Each of the associating hetero-oligomeric receptor pairs generated a BRET signal of similar intensity, less than that of homo-oligomeric secretin receptors. BRET signals from some receptor pairs were reduced by ligand occupation, but none were increased by this treatment. Thus, Family B GPCR oligomerization occurs, with many structurally related members associating with each other. The specific functional implications of this need to be further evaluated.
KW - Bioluminescence resonance energy transfer
KW - Fluorescence resonance energy transfer
KW - G-protein-coupled receptors
KW - Heteroligomerization
KW - Secretin receptor
KW - Surface expression
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U2 - 10.1007/s12031-008-9060-z
DO - 10.1007/s12031-008-9060-z
M3 - Article
C2 - 18401761
AN - SCOPUS:58149097996
SN - 0895-8696
VL - 36
SP - 279
EP - 285
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
IS - 1-3
ER -