Gustducin - Evolution of The Gustducin-mediated Signaling Model

Evolution of The Gustducin-mediated Signaling Model

While gustducin was known to be expressed in taste cells, studies with rats showed that gustducin was also present in a limited subset of cells lining the stomach and intestine. These cells appear to share several feature of taste receptor cells. Another study with humans brought to light two immunoreactive patterns for α-gustducin in human circumavallate and foliate taste cells: plasmalemmal and cytosolic. These two studies showed that gustducin is distributed through gustatory tissue and some gastric and intestinal tissue and gustducin is presented in either a cytoplasmic or apical pattern.

Due to its structural similarity to transducin, gustducin was predicted to activate a phosphodiesterase (PDE). Phosphodieterases were found in taste tissues and their activation was tested in vitro with both gustducin and transducin. This experiment revealed transducin and gustducin were both expressed in taste tissue (1:25 ratio) and that both G proteins are capable of activating retinal PDE. Furthermore, when present with denatonium and quinine, both G proteins can activate taste specific PDEs. This indicated that both gustducin and transducin are important in the signal transduction of denatonium and quinine.

Finally, Margolskee’s group investigated the role of gustducin in bitter taste reception by using “knock-out” mice lacking the gene for α-gustducin. A taste test with knock-out and control mice revealed that the knock-out mice showed no preference between bitter and regular food in most cases. When the α-gustducin gene was re-inserted into the knock-out mice, the original taste ability returned. However, the loss of the α-gustducin gene did not completely remove the ability of the knock-out mice to taste bitter food. This indicates that α-gustducin is not the only mechanism for tasting bitter food. It was thought, though unconfirmed, that an alternative mechanism of bitter taste detection could be associated with the βγ subunit of gustducin. This theory was validated when it was discovered that both peripheral and central gustatory neurons typically respond to more than one type of taste stimulant, although a neuron typically would favor one specific stimulant over others. This suggests that, while many neurons favor bitter taste stimuli, neurons that favor other stimuli such as sweet and umami may be capable of detecting bitter stimuli in the absence of bitter stimulant receptors, as with the knock-out mice.