Table

The special case of the Serpentine receptors.

A particularly interesting and important class of cell-surface signal receptors are those known as the seven-transmembrane G protein-coupled receptors (7TM-GPCRs, or 7TMRs). There are hundreds of genes in this class, involved in diverse aspects of information transfer to cells. As shown in Scheme 7-2, these receptor molecules contain seven helical transmembrane domains, with additional extra- and intracellular domains.

Transmembrane information transfer that relies on secondary messengers often involves G protein cascades. G protein-coupled cell surface receptors (GPCRs) are a large and ancient class of seven transmembrane receptors, cellular signaling mechanisms found in many different kinds of receptor-ligand interactions in a wide range of cell types and organisms, including single-celled yeast (the receptors for yeast mating factors are an example) (Alberts 1994). In vertebrates, close to 2,000 GPCRs have been identified, including more than 1,000 for odorant and pheromone detection alone. About 1,100 GPCRs are known in C. elegans (Bockaert and Pin 1999).

When GPCRs are compared at the amino acid level, by phylogenetic relationship and the type of ligand to which they can bind, they cluster in at least six main families; GPCRs from the different families show little sequence homology at the DNA level (GPCR 2003; Bockaert and Pin 1999). These tentative groups are itemized in Table 7-4. Class I GPCRs constitute the largest and includes many small peptide or weakly hydrophobic organic molecules. This class is basically for chemoreception and chemotaxis and includes olfactory and taste receptors, for which the ligands are weakly hydrophobic, organic molecules, or small peptides. Class II GPCRs antedate the protostome-deuterostome divergence, and this class comprises receptors for biogenic amines (acetylcholine, catecholamine, and indoleamine) largely related to neurological function. Class III genes include small neuropeptide receptors and receptors for chromophores (vertebrate visual pigments); these are the opsins used in light sensing. Class IV genes are insect and molluscan opsins, which bind to small odorant molecules of various types. Class V genes are receptors for small hormone molecules of various kinds that are involved in immune chemotaxis and blood-clotting; these genes are also involved in the secretion of steroid hormones. In vertebrates, some similar neurological and endocrine peptides are mediated by singletransmembrane receptors. Class VI GPCRs are members of the smoothened/frizzled family of vomeronasal receptors.

Additional GPCRs continue to be found and classified. No amino acids are conserved among all the classes of these genes, and few are conserved even among many. Within a given class, a relatively small number of sites determine the receptors' specificity to ligands.

GPCRs set into motion a chain of events that alter the concentration of intracellular signaling molecules, which in turn affect the behavior of other cellular components. Most G protein cascades involve alterations in the cellular concentrations of cAMP, cGMP, or Ca2+, which induces activation of an effector molecule that produces a response specific to the receptor and cell type. This system is common in but not restricted to sensory perception; regulation of heart rate, contraction of smooth muscle, and secretion of hormones or growth factors are examples of other systems that use this mechanism. The effects can be achieved in various ways, including the regulation of membrane ion transport channels, transmission of signal pulses to adjacent cells as in the transmission of nerve impulses from retinal neurons, or the regulation of transcription factors. Similar mechanisms are fundamental or even ubiquitously used for the transfer of cell-differentiating signals in both plant and animal development (Chapter 8).

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