Summary of Wenner-Gren international symposium receptor-receptor interactions among heptaspanning membrane receptors: from structure to function.

Listening to the talks delivered at the symposium during this 2 1/2-d meeting left me with the feeling that this was a field that has truly come of age in the past few years. Although the earliest observations, a number of them by the organizers of the meeting, on receptor-receptor interactions go back almost two decades, it is really only in the past few years that the molecular basis of these interactions has begun to be clarified. The initial skepticism is now subsiding as more and more examples of receptor oligomerization are identified. At the meeting, three types of receptor oligomerization were discussed: homo-oligomerization; hetero-oligomerization, where both partners are seven transmembrane (7TM)-spanning receptors; and hetero-oligomerization, where a 7 TM-spanning receptor is complexed with a structurally different class of molecule. Although interesting papers were presented in each area, I found myself most intrigued by the papers dealing with hetero-oligomerization between different 7TM-spanning receptors. Most striking were examples where novel functions were created by the heterodimerization process, such as novel opioid binding patterns or the acquisition of novel signaling pathways, as in the case of D1-D2 dopamine receptor heterodimerization. In this connection, to me, one of the most interesting discussions concerned the possibility that a number of currently so-called orphan receptors might have no personal ligands but, rather, function to bestow novel properties on other 7TM-spanning receptors by oligomer formation. Thus, these orphans might convey a new signaling function or an altered ligand- binding specificity on a known receptor. If this were the case then, for such an orphan, all efforts to identify its function by expressing it alone would be doomed to fail. Another potentially interesting function of some orphan receptors might be to act as chaperones for other receptors, helping to bring them to the cell surface and stabilizing their membrane expression.

Duke Scholars

Author Robert J. Lefkowitz Medicine, Cardiology