Table 75


Of the GPCRs that modulate cyclic nucleotides, some regulate adenylate cyclase activity. Activation of adenylyl cyclase leads to the production of cAMP as a second messenger, and cAMP in turn leads to the activation of ion channels. Odorant receptors are an example of this type of GPCR. Photoreceptors are a class of GPCR coupled to the G protein transducin, which activates phosphodiesterase, an enzyme that causes a drop in the level of cGMP, which leads to the closing of sodium and calcium channels and hyperpolarization (an increase in the negative charge) of the cell.

These are general, stereotypical descriptions. Not all aspects of all of these many genes have been carefully checked. Some things are reasonably well-studied, however. The ligand binding characteristics differ among genes and among classes and will be discussed in several places in this book. The point is that receipt of an odorant by an olfactory receptor GPCR is "wired" to the olfactory part of the brain, whereas the receipt of a photon by a chromophore GPCR ligand is wired to the visual system. We have given this brief summary of this class of genes because its members are used in so many diverse ways relevant to this book and because it is central to communication between a cell and its outside world. But it is the logic and modular nature of the various uses of these common signal-related molecules that is of importance here. For biochemical details, seek appropriate sources.

Regulation of Gene Expression

Signaling between cells may affect a variety of functions. Usually this means changes in gene expression in the receiving cell, which implies that the signal causes the activation or inactivation of one or more TFs. There are several TF gene families (Table 7-6), characterized by their DNA binding domains of their coded protein. The most famous of these is the homeobox after which a major TF class is named. The home-obox is a region coding for a 60-amino acid homeodomain (so called because of the effect discovered in the 1980s when mutations in these genes produced famous replicated or altered segmental structures in flies). Each of the many subclasses of home-obox genes shares one or more variants in the homeodomain, and they bind to somewhat different response or regulatory element (RE) sequences; however, as a rule, this region of the class of genes is much less variable than other active domains, and there is a lot of sharing of the binding sequence (e.g., TAAT) among homeobox genes; the other domains are more varied and have different functions, not all of which are known (Alberts 1994; Transfac 2003).

CHAPTERS 4-5-6-7: COMPLEX TRAITS REVISITED Signaling and gene regulation are so fundamental to complex organisms that we can expect there to be an elaborate set of mechanisms, and there are. We can now look at them in light of concepts covered in this and previous chapters. The importance of the modular organization of the genome and the various information encoded in DNA sequence is clear.

The major classes of genes for signaling appear to have evolved from multiple essentially independent beginnings. However, the logic of signaling mechanisms

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