Serpentine Receptors

Seven transmembrane helix receptors Heptahelical receptors Serpentine receptors... 

The common feature of this superfamily (there are many different families and subtypes of receptors in this group) of receptors is that there are seven domains that cross the cell membrane (Fig. 2.6). These seven transmembrane receptors are often referred to as serpentine receptors. 

Brown, E. M., Segre, G. V., and Goldring, S. R. (1996) Serpentine receptors for parathyroid hormone, calcitonin and extracellular calcium ions. Baillieres Best Pract. Res. Clin. Endocrinol. Metab. 10, 123-161. 

Helix receptors (serpentine receptors, right) represent a large group of membrane proteins that transfer the hormone or transmitter signal,with the helpofGproteins(see below), to effector proteins that alter the concentrations of ions and second messengers (see B). 

Due to the common appearance of 7 transmembrane helices, the family of G-protein coupled receptors is also known as the family of the 7-helix transmembrane receptors. The G-protein coupled receptors are also sometimes called the serpentine receptors, pointing to the serpentine-like configuration of transmembrane hehces. 

Serpentine receptor kinase P-adrenergic receptor kinase, PARK... 

For the 3 adrenoceptor, and many other serpentine receptors, 3-arrestin binding also accelerates endocytosis of receptors from the plasma membrane. Endocytosis of receptors promotes their dephosphorylation, by a receptor phosphatase that is present at high concentration on endosome membranes, and receptors then return to the plasma membrane. This helps explain the ability of cells to recover receptor-mediated signaling responsiveness very efficiently after agonist-induced desensitization. 

Several serpentine receptors—including the E> adrenoceptor if it is persistently activated—instead traffic to lysosomes after endocytosis and are degraded. This process effectively attenuates (rather than restores) cellular responsiveness, similar to the process of down-regulation described above for the epidermal growth factor receptor. Thus, depending on the particular receptor and duration of activation, endocytosis can contribute to either rapid recovery or prolonged attenuation of cellular responsiveness (Figure 2-12). 

Receptor proteins (serpentine receptors) that indirectly activate (through GTP-binding proteins, or G proteins) enzymes that generate intracellular second messengers. This is illustrated by the /3-adrenergic receptor system that detects epinephrine (adrenaline) (Section 12.4). 

The /3-adrenergic receptor is an integral protein with seven hydrophobic regions of 20 to 28 amino acid residues that snake back and forth across the plasma membrane seven times. This protein is a member of a very large family of receptors, all with seven transmembrane helices, that are commonly called serpentine receptors, G protein-coupled receptors (GPCR), or 7 transmembrane segment (7tm) receptors. The binding of epinephrine to a site on the... 

FIGURE 12-18 /3-Arrestin uncouples the serpentine receptor from its G protein and brings together the three enzymes of the MAPK cascade. The effect is that one stimulus triggers two distinct response pathways the path activated by the G protein and the MAPK cascade. 

A second class of serpentine receptors are coupled through a G protein to a plasma membrane phospholipase C (PLC) that is specific for the plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (see Fig. 10-15). This hormone-sensitive enzyme catalyzes the formation of two potent second messengers diacyl-glycerol and inositol 1,4,5-trisphosphate, or IP i (not to be confused with PIP3, p. 431). 

G Protein-Coupled Serpentine Receptor Systems Share Several Features... 

TABLE 12-8 Some Signals Transduced by G Protein-Coupled Serpentine Receptors... 

Vision, olfaction, and gustation in vertebrates employ serpentine receptors, which act... 

In olfactory neurons, olfactory stimuli, acting through serpentine receptors and G proteins, trigger either an increase in [cAMP] (by activating adenylyl cyclase) or an increase in [Ca2+] (by activating PLC). These second messengers affect ion channels and thus the Vm. 

Gustatory neurons have serpentine receptors that respond to tastants by altering [cAMP], which in turn changes Vm by gating ion channels. 

The family of G proteins contains several functionally diverse subfamilies (Table 2-2), each of which mediates effects of a particular set of receptors to a distinctive group of effectors. Receptors coupled to G proteins comprise a family of "seven-transmembrane" or "serpentine" receptors, so called because the receptor polypeptide chain "snakes" across the plasma membrane seven times (Figure 2-11). Receptors for adrenergic amines, serotonin, acetylcholine (muscarinic but not... 

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