Figure 15–36 Olfactory receptor neurons. (A) A section of olfactory epithelium in the nose. Olfactory receptor neurons possess modified cilia, which project from the surface of the epithelium and contain the olfactory receptors, as well as the signal transduction machinery. The axon, which extends from the opposite end of the receptor neuron, conveys electrical signals to the brain when an odorant activates the cell to produce an action potential. In rodents, at least, the basal cells act as stem cells, producing new receptor neurons throughout life, to replace the neurons that die. (B) A scanning electron micrograph of the cilia on the surface of an olfactory neuron. (B, from
E.E.
Morrison and R.M. Costanzo,
J.
Comp. Neurol. 297:1–13, 1990. With permission from Wiley-Liss.)
H2NNNNHNCH2OOOHOO_OPGUANINEPHOSPHATESUGAROFigure 15–37 Cyclic GMP.
Figure 15–38 A rod photoreceptor cell. There are about 1000 discs in the outer segment. The disc membranes are not connected to the plasma membrane. The inner and outer segments are specialized parts of a primary cilium (discussed in Chapter 16). A primary cilium extends from the surface of most vertebrate cells, where it serves as a signaling organelle.
Rhodopsin is a member of the GPCR family, but the activating extracellular signal is not a molecule but a photon of light. Each rhodopsin molecule contains a covalently attached chromophore, 11-cis retinal, which isomerizes almost instantaneously to all-trans retinal when it absorbs a single photon. The isomerization alters the shape of the retinal, forcing a conformational change in the protein (opsin). The activated rhodopsin molecule then alters the conformation of the G protein transducin (Gt), causing the transducin α subunit to activate cyclic GMP phosphodiesterase. The phosphodiesterase then hydrolyzes cyclic GMP, so that cyclic GMP levels in the cytosol fall. This drop in cyclic GMP concentration decreases the amount of cyclic GMP bound to the plasma membrane cation channels, allowing more of these cyclic-GMP-sensitive channels to close. In this way, the signal quickly passes from the disc membrane to the plasma membrane, and a light signal is converted into an electrical one, through a hyperpolarization of the rod cell plasma membrane.
Rods use several negative feedback loops to allow the cells to revert quickly to a resting, dark state in the aftermath of a flash of light—a requirement for perceiving the shortness of the flash. A rhodopsin-specific protein kinase called rhodopsin kinase (RK) phosphorylates the cytosolic tail of activated rhodopsin on multiple serines, partially inhibiting the ability of the rhodopsin to activate transducin. An inhibitory protein called arrestin (discussed later) then binds to the phosphorylated rhodopsin, further inhibiting rhodopsin’s activity. Mice or humans with a mutation that inactivates the gene encoding RK have a prolonged light response.
At the same time as arrestin shuts off rhodopsin, an RGS protein (discussed earlier) binds to activated transducin, stimulating the transducin to hydrolyze its bound GTP to GDP, which returns transducin to its inactive state. In addition, the cation channels that close in response to light are permeable to Ca2+, as well as high rate of low rate of (signals to discs of photoreceptive outer