Gustducin
guanine nucleotide binding protein, alpha transducing 3 | |||||||
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Chr. 7 q21.11 | |||||||
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guanine nucleotide binding protein (G protein), beta polypeptide 1 | |||||||
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Identifiers | |||||||
Symbol | GNB1 | ||||||
Chr. 1 p36.33 | |||||||
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guanine nucleotide binding protein (G protein), gamma 13 | |||||||
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Identifiers | |||||||
Symbol | Chr. 16 p13.3 | ||||||
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Gustducin is a
An intriguing feature of gustducin is its similarity to transducin. These two G proteins have been shown to be structurally and functionally similar, leading researchers to believe that the sense of taste evolved in a similar fashion to the sense of sight.
Gustducin is a heterotrimeric protein composed of the products of the GNAT3 (α-subunit), GNB1 (β-subunit) and GNG13 (γ-subunit).
Discovery
Gustducin was discovered in 1992 when degenerate
Comparisons with transducin
Upon analyzing the
However, the two proteins have similar mechanism and capabilities. Transducin removes the inhibition from cGMP Phosphodiesterase, which leads to the breakdown of cGMP. Similarly, α-gustducin binds the inhibitory subunits of taste cell cAMP Phosphodiesterase which causes a decrease in cAMP levels. Also, the terminal 38 amino acids of α-gustducin and α-transducin are identical. This suggests that gustducin can interact with opsin and opsin-like G-coupled receptors. Conversely, this also suggests that transducin can interact with taste receptors.
The structural similarities between gustducin and transducin are so great that comparison with transducin were used to propose a model of gustducin's role and functionality in taste transduction.[citation needed]
Other G protein α-subunits have been identified in TRCs (e.g. Gαi-2, Gαi-3, Gα14, Gα15, Gαq, Gαs) with function that has not yet been determined.[2]
Location
While gustducin was known to be expressed in some taste receptor cells (TRCs), 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 TRCs. Another study with humans brought to light two immunoreactive patterns for α-gustducin in human circumavallate and foliate taste cells:
Research showed that bitter-stimulated type 2 taste receptors (T2R/TRB) are only found in taste receptor cells positive for the expression of gustducin. α-Gustducin is selectively expressed in ~25–30% of TRCs [2]
Evolution of the gustducin-mediated signaling model
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.
The 1992 research also 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
However, the loss of the α-gustducin gene did not completely remove the ability of the knock-out mice to taste bitter food, indicating that α-gustducin is not the only mechanism for tasting bitter food. It was thought at the time that an alternative mechanism of bitter taste detection could be associated with the βγ subunit of gustducin. This theory was later 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.[citation needed]
Second messengers IP3 and cAMP
Until recently, the nature of gustducin and its
Bitter transduction
When bitter-stimulated T2R/TRB receptors activate gustducin heterotrimers, gustducin acts to mediate two responses in taste receptor cells: a decrease in cAMPs triggered by α-gustducin, and a rise in IP3(Inositol trisphosphate) and diacylglycerol (DAG) from βγ-gustducin.[2]
Although the following steps of the α-gustducin pathway are unconfirmed, it is suspected that decreased cAMPs may act on protein kinases which would regulate taste receptor cell ion channel activity. It is also possible that cNMP levels directly regulate the activity of cNMP-gated channels and cNMP-inhibited
Bitter taste transduction models Several models have been suggested for the mechanisms regarding the transduction of bitter taste signals.
- Cell-surface receptors: Patch clamping experiments have shown evidence that bitter compounds such as denatonium and sucrose octaacetate act directly on specific cell-surface receptors.[citation needed]
- Direct activation of G proteins: Certain bitter stimulants such as quinine have been shown to activate G proteins directly. While these mechanisms have been identified,[by whom?] the physiologic relevance of the mechanism has not yet been established.
- PDE activation: Other bitter compounds, such as thioacetamide and propylthiouracil, have been shown[by whom?] to have stimulatory effects on PDEs. This mechanism has been recognized in bovine tongue epithelium contains fungiform papillae.
- PDE inhibition: Other bitter compounds have been shown[by whom?] to inhibit PDE. Bacitracin and hydrochloride have been shown to inhibit PDE in bovine taste tissue
- Channel blockage: Patch clamping experiments have shown that several bitter ions act directly on potassium channels, blocking them. This suggests that the mudpuppytaste cells.
It is thought[by whom?] that these five diverse mechanisms have developed as defense mechanisms. This would imply that many different poisonous or harmful bitter agents exist and these five mechanisms exist to prevent humans from eating or drinking them. It is also possible that some mechanisms can act as backups should a primary mechanism fail. One example of this could be quinine, which has been shown to both inhibit and activate PDE in bovine taste tissue.
Sweet transduction
There are currently two models proposed for sweet taste transduction. The first pathway is a
The second pathway is a GPCR-Gq/Gβγ-IP3 pathway which is used with artificial sweeteners. Artificial sweeteners bind and activate GPCRs coupled to PLCβ2 by either α-Gq or Gβγ. The activated subunits activate PLCβ2 to generate IP3 and DAG. IP3 and DAG elicit
Evolution of bitter taste receptors
Of the five
Gustducin in the stomach
Recent work by Enrique Rozengurt has shed some light on the presence of gustducin in the stomach and gastrointestinal tract.[3] His work suggests that gustducin is present in these areas as a defense mechanism. It is widely known that some drugs and toxins can cause harm and even be lethal if ingested. It has already been theorized that multiple bitter taste reception pathways exist to prevent harmful substances from being ingested, but a person can choose to ignore the taste of a substance. Ronzegurt suggests that the presence of gustducin in epithelial cells in the stomach and gastrointestinal tract are indicative of another line of defense against ingested toxins. Whereas taste cells in the mouth are designed to compel a person to spit out a toxin, these stomach cells may act to force a person to spit up the toxins in the form of vomit.
See also
- transducin
- gustatory system
References
Further reading
- Hoon MA, Northup JK, Margolskee RF, Ryba NJ (July 1995). "Functional expression of the taste specific G-protein, alpha-gustducin". Biochem. J. 309. ( Pt 2) (2): 629–36. PMID 7626029.
- Fischer A, Gilad Y, Man O, Pääbo S (March 2005). "Evolution of bitter taste receptors in humans and apes". Mol. Biol. Evol. 22 (3): 432–6. PMID 15496549.
- Lindemann B (October 1996). "Chemoreception: tasting the sweet and the bitter". Curr. Biol. 6 (10): 1234–7. S2CID 17234116.
- Lindemann B (April 1999). "Receptor seeks ligand: on the way to cloning the molecular receptors for sweet and bitter taste". Nat. Med. 5 (4): 381–2. S2CID 5650076.
- Margolskee RF (January 2002). "Molecular mechanisms of bitter and sweet taste transduction". J. Biol. Chem. 277 (1): 1–4. PMID 11696554.
- Spielman AI (April 1998). "Gustducin and its role in taste". J. Dent. Res. 77 (4): 539–44. S2CID 28730822.
- Smith DV, Margolskee RF (March 2001). "Making sense of taste". Sci. Am. 284 (3): 32–9. PMID 11234504.
- Wong GT, Gannon KS, Margolskee RF (June 1996). "Transduction of bitter and sweet taste by gustducin". Nature. 381 (6585): 796–800. S2CID 4232354.
External links
- Gustducin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)