Molecular Basis Of Ecdysteroid Signaling

Ecdysteroids belong to a large class of steroid chemical signaling molecules. Because of their lipophilic character, they pass through the cell membrane easily. Whether they affect the cell upon entry depends on the presence or absence of specialized proteins belonging to a large class of soluble, diffusible nuclear receptors. Nuclear receptors get their name from the part of the cell in which they conduct their business, which is the regulation of gene expression. Early in the 1990s, David Hogness and colleagues discovered in fruit flies a class of nuclear receptors they called EcRs. Upon their activation by ecdysone binding, EcRs bind directly to DNA at "ecdysone response elements" (EcRs) to turn genes on or off. Further work showed that to bind with high affinity to DNA, the EcR first finds a partner protein to form a doublet, or "dimer" complex. It is this protein dimer that, together with coactivator proteins, binds to EcREs, resulting in regulation of gene expression.

It is well known that EcRs affect cells in many different ways, causing some to differentiate into muscles and some into glands, and others to form particular kinds of cuticle and cuticular structures appropriate for a larva, a pupa, or an adult. The process by which ecdysteroid receptors encode this diversity of effects is very complicated, and many questions are under current investigation. But it is known already that several different types of ecdysteroid receptor occur in insects, including EcRA, EcrBl, and EcRB2. These receptor "subtypes" occur at different stages of development and can be specific to particular tissues. Thus at least some of the stage-specific effects seem to depend on this diversity of receptors. Another point is that the partners with which they bind to DNA probably vary substantially, providing a further level of combinatorial diversity.

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