| DO ORPHAN RECEPTORS HAVE LIGANDS? |
| A Site Map of the Debate
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The biological actions of hormones such as estrogen, testosterone and thyroid hormone, as well as certain vitamins including A and D, involve uptake into cells and binding to specific proteins called receptors. Binding of each hormone or vitamin (i.e., each ligand) to its receptor activates it, enabling the receptor to regulate cell function. Recently biologists have identified many proteins that are structurally similar to the intracellular hormone/vitamin receptors. Certain of these proteins have no known ligand activators, and are therefore called orphan receptors. Researchers are now faced with the questions "Do all the orphan receptors have ligands, or are some members of this protein family activated by other cellular mechanisms?" and "How can we identify the ligands for the orphan receptors?"
The answers to these questions will provide fundamental information about how different types of cells in our bodies communicate with each other. In addition, identifying ligands for orphan receptors should provide a wealth of new pharmaceutical agents.
The DebateThe second in our series of debate took place during the week of February 3, asking whether the orphan receptors are truly ligand-independent transcriptional regulators, or whether many or all have ligands that remain to be identified. Three participants and a moderator address the issue of what criteria are useful for distinguishing ligand-activited from ligand-independent activation of the orphan nuclear receptors, and what strategies may be useful for identifying ligand for the orphans.
The debate was opened a with general introduction, provided by the moderator, Dr. Mitchell Lazar, at the beginning of the Day 1 folder. Each day a new folder representing a new subtopic, was opened for posting messages; these folders remained open all week (and beyond) so that participants could extend their discussions on the topics therein.
It should be noted that the Day 4 folder covers criteria for establishing a systematic nomenclature for the orphan receptors. This gives the discussants? attempt at consensus, but leaves the task unfinished. Interested parties should help complete the project by joining our Readers Discussion via the BioMedNet discussion group. You may respond to this issue or any others raised (or omitted) in the debate by clicking either the Feedback or the Discussion icons below.
Debate DocumentsHere in the Cutting Edge section we have assembled some introductory documents and a synopsis of the debate, as well as the full text of the debate document (also available to view or download as a PDF file). The listing of references reflects all citations in the debate, as well as recommended background reading that may be viewed or downloaded in full, at no charge, from the BioMedNet Library by HMS Beagle readers. Most cited references are linked to abstracts in Entrez Medline.
See our previous debate on the Origin and Evolution of Introns, moderated by Russ Doolittle. You can also check out our archive of cutting edge debates and dialogs.