Transient receptor potential
Encyclopedia
Transient receptor potential channels (TRP channels) are a group of ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...

s located mostly on the plasma membrane of numerous human and animal cell types. There are about 28 TRP channels that share some structural similarity to each other. These are grouped into two broad groups: group 1 includes, TRPC
TRPC
TRPC is a family of transient receptor potential cation channels in animals.TRPC channels form the subfamily of channels in human most closely related to drosophila TRP channels. In terms of structure, this family possesses a number of similar characteristics...

 ( "C" for canonical), TRPV
TRPV
TRPV is a family of transient receptor potential ion channels. These channels are selective for calcium and magnesium over sodium ions. Like other members of the TRP superfamily, TRPV channels can be activated through seemingly disparate mechanisms...

 ("V" for vanilloid), TRPM
TRPM
TRPM is a family of transient receptor potential ion channels . Functional TRPM channels are believed to form tetramers....

 ("M" for melastatin), TRPN and TRPA
TRPA (channel)
TRPA is a family of transient receptor potential ion channels.The sole member of the TRPA sub-family, TRPA1, contains 14 N-terminal ankyrin repeats and is believed to function as a mechanical stress sensor. It is expressed in the dorsal root ganglion, trigeminal ganglion, and hair cells...

. In group 2 there are TRPP
TRPP
TRPP is a family of transient receptor potential ion channels which when mutated can cause polycystic kidney disease.-Subcategories:...

 ("P" for polycystic) and TRPML
TRPML
TRPML comprises a group of three evolutionary related proteins that belongs to the large family of transient receptor potential ion channels...

 ("ML" for mucolipin). Many of these channels mediate a variety of sensations like the sensations of pain, hotness, warmth or coldness, different kinds of tastes, pressure, and vision. In the body, some TRP channels are thought to behave like microscopic thermometers and used in animals to sense hot or cold. Some TRP channels are activated by molecules found in spices like garlic (allicin), chilli pepper (capsaicin
Capsaicin
Capsaicin 2CHCH=CH4CONHCH2C6H3-4--3- ) is the active component of chili peppers, which are plants belonging to the genus Capsicum. It is an irritant for mammals, including humans, and produces a sensation of burning in any tissue with which it comes into contact...

), wasabi (allyl isothiocyanate
Allyl isothiocyanate
Allyl isothiocyanate is the organosulfur compound with the formula CH2CHCH2NCS. This colorless oil is responsible for the pungent taste of mustard, horseradish, and wasabi. This pungency and the lachrymatory effect of AITC is mediated through the TRPA1 and TRPV1 ion channels...

); others are activated by menthol
Menthol
Menthol is an organic compound made synthetically or obtained from peppermint or other mint oils. It is a waxy, crystalline substance, clear or white in color, which is solid at room temperature and melts slightly above. The main form of menthol occurring in nature is -menthol, which is assigned...

, camphor
Camphor
Camphor is a waxy, white or transparent solid with a strong, aromatic odor. It is a terpenoid with the chemical formula C10H16O. It is found in wood of the camphor laurel , a large evergreen tree found in Asia and also of Dryobalanops aromatica, a giant of the Bornean forests...

, peppermint, and cooling agents; yet others are activated by molecules (THC
THC
THC commonly refers to tetrahydrocannabinol, the main active chemical compound in Cannabis.THC may also refer to:* Tan Holdings Corporation...

, CBD
Carbohydrate-binding module
In molecular biology, a carbohydrate-binding module is a protein domain found in carbohydrate-active enzymes . The majority of these domains have carbohydrate-binding activity. Some of these domains are found on cellulosomal scaffoldin proteins. CBMs were previously known as cellulose-binding...

 and CBN
Cannabinol
Cannabinol is a psychoactive substance cannabinoid found in Cannabis sativa and Cannabis indica/afghanica. It is also a metabolite of tetrahydrocannabinol . CBN acts as a weak agonist of the CB1 and CB2 receptors, with lower affinity in comparison to THC.- External links :* Compounds found in...

) found in marijuana. Some act as sensors of osmotic pressure, volume, stretch, and vibration.

These ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...

s are relatively non-selectively permeable to cations, including sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

, calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

 and magnesium
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...

. TRP channels were initially discovered in trp mutant strain of the fruit fly Drosophila
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...

. Later, TRP channels were found in vertebrates where they are ubiquitously expressed in many cell types and tissues. Most TRP channels are composed of 6 membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

-spanning helices with intracellular N- and C-termini. Mammalian TRP channels are activated and regulated by a wide variety of stimuli and are expressed throughout the body.

Sub-families

They are encoded by at least 33 channel subunit gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

s divided into seven sub-families:
  • TRPC
    TRPC
    TRPC is a family of transient receptor potential cation channels in animals.TRPC channels form the subfamily of channels in human most closely related to drosophila TRP channels. In terms of structure, this family possesses a number of similar characteristics...

     (canonical) - associated with Focal segmental glomerulosclerosis
    Focal segmental glomerulosclerosis
    Focal segmental glomerulosclerosis is a cause of nephrotic syndrome in children and adolescents, as well as an important cause of kidney failure in adults.It is also known as "focal glomerular sclerosis" or "focal nodular glomerulosclerosis"....

  • TRPV
    TRPV
    TRPV is a family of transient receptor potential ion channels. These channels are selective for calcium and magnesium over sodium ions. Like other members of the TRP superfamily, TRPV channels can be activated through seemingly disparate mechanisms...

     (vanilloid)
  • TRPA
    TRPA (channel)
    TRPA is a family of transient receptor potential ion channels.The sole member of the TRPA sub-family, TRPA1, contains 14 N-terminal ankyrin repeats and is believed to function as a mechanical stress sensor. It is expressed in the dorsal root ganglion, trigeminal ganglion, and hair cells...

     (ankyrin)
  • TRPM
    TRPM
    TRPM is a family of transient receptor potential ion channels . Functional TRPM channels are believed to form tetramers....

     (melastatin) -- associated with Hypomagnesemia with secondary hypocalcemia
    Hypomagnesemia with secondary hypocalcemia
    Hypomagnesemia with secondary hypocalcemia is an autosomal recessive genetic disorder affecting intestinal magnesium absorption. Decreased intestinal magnesium reabsorption and the resulting decrease in serum magnesium levels is believed to cause lowered parathyroid hormone output by the...

  • TRPP
    TRPP
    TRPP is a family of transient receptor potential ion channels which when mutated can cause polycystic kidney disease.-Subcategories:...

     (polycystin) -- associated with Polycystic kidney disease
    Polycystic kidney disease
    Autosomal dominant polycystic kidney disease is an inherited systemic disorder that predominantly affects the kidneys, but may affect other organs including the liver, pancreas, brain, and arterial blood vessels...

  • TRPML
    TRPML
    TRPML comprises a group of three evolutionary related proteins that belongs to the large family of transient receptor potential ion channels...

     (mucolipin) -- associated with Mucolipidosis type IV
    Mucolipidosis type IV
    Mucolipidosis type IV is an autosomal recessive lysosomal storage disorder. Individuals with the disorder have many symptoms including delayed psychomotor development and various ocular aberrations. The disorder is caused by mutations in the MCOLN1 gene, which encodes a non-selective cation...

  • TRPN (NOMPC) - no mechanoreceptor potential C - not found in mammals

TRP-like channels in insect vision

The trp mutant fruit flies, that lack a functional copy of trp gene, are characterized by a transient response to light unlike wild-type flies that demonstrate a sustained photoreceptor cell activity in response to light.
A distantly related isoform of TRP channel, TRP-like channel (TRPL) was later identified in Drosophila photoreceptors, where it is expressed at approximately 10 to 20-fold lower levels than TRP protein. A mutant fly, trpl, was subsequently isolated. Apart from structural differences, the TRP and TRPL channels differ in cation permeability and pharmacological properties.

TRP/TRPL channels are solely responsible for depolarization of insect photoreceptor plasma membrane in response to light. When these channels open, they allow sodium and calcium to enter the cell down the concentration gradient, which depolarizes the membrane. Variations in light intensity affect the total number of open TRP/TRPL channels, and, therefore the degree of membrane depolarization. These graded voltage responses propagate to photoreceptor synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...

s with second-order retinal neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s and further to the brain.

Importantly, the mechanism of insect photoreception is dramatically different from that in mammals. Excitation of rhodopsin in mammalian photoreceptors leads to the hyperpolarization of the receptor membrane but not to depolarization like in the insect eye. In Drosophila and presumably other insects, a phospholipase C (PLC)-mediated signaling cascade links photoexcitation of rhodopsin
Rhodopsin
Rhodopsin, also known as visual purple, is a biological pigment of the retina that is responsible for both the formation of the photoreceptor cells and the first events in the perception of light. Rhodopsins belong to the G-protein coupled receptor family and are extremely sensitive to light,...

 to the opening of the TRP/TRPL channels. Although numerous activators of these channels such as phosphatidylinositol-4,5-bisphosphate (PIP2) and polyunsaturated fatty acids (PUFAs) were known for years, a key factor mediating chemical coupling between PLC and TRP/TRPL channels remained a mystery until recently. It was found that breakdown of a lipid product of PLC cascade, diacylglycerol (DAG), by the enzyme Diacylglycerol lipase
Diacylglycerol lipase
Diacylglycerol lipase, also known as DAG lipase, DAGL or DGL, is a key enzyme in the biosynthesis of the endocannabinoid 2-arachidonoylglycerol. It catalyzes the hydrolysis of diacylglycerol, releasing a free fatty acid and monoacylglycerol....

, generates PUFAs that can activate TRP channels thus initiating membrane depolarization in response to light. This mechanism of TRP channel activation may be well preserved among other cell types where these channels perform various functions.

History of Drosophila TRP channels

The original TRP mutant in Drosophila was first described by Cosens and Manning in 1969 as a "a mutant strain of D. melanogaster which, though behaving phototactically positive in a T-maze under low ambient light, is visually impaired and behaves as though blind". It also showed an abnormal ERG response to light and it was investigated subsequently by Baruch Minke, a post-doc in the group of William Pak, and named TRP according to its behavior in the ERG. The identity of the mutated protein was unknown until it was cloned by Craig Montell, a post doctoral researcher in Gerald Rubin's research group, in 1989, who noted its predicted structural relationship to channels known at the time and Roger Hardie and Baruch Minke who provided evidence in 1992 that it was an ion channel that opened in response to light stimulation. The TRPL channel was cloned and characterized in 1992 by the research group of Leonard Kelly.
The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
x
OK