Transient receptor potential channel

Transient receptor potential (TRP) ion channel
Identifiers
Symbol TRP
Pfam PF06011
InterPro IPR010308

Transient receptor potential channels (TRP channels) are a group of ion channels 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.[1] These are grouped into two broad groups: group 1 includes, TRPC ( "C" for canonical), TRPV ("V" for vanilloid), TRPM ("M" for melastatin), TRPN and TRPA. In group 2 there are TRPP ("P" for polycystic) and TRPML ("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), wasabi (allyl isothiocyanate); others are activated by menthol, camphor, peppermint, and cooling agents; yet others are activated by molecules (THC, CBD and CBN) found in marijuana. Some act as sensors of osmotic pressure, volume, stretch, and vibration.

These ion channels are relatively non-selectively permeable to cations, including sodium, calcium and magnesium. TRP channels were initially discovered in trp mutant strain of the fruit fly Drosophila. 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-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.

Contents

Sub-families

They are encoded by at least 33 channel subunit genes divided into seven sub-families:

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.[2] 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 synapses with second-order retinal neurons 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 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, generates PUFAs that can activate TRP channels thus initiating membrane depolarization in response to light.[3] 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[4] 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.[2] 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 [5] and Roger Hardie and Baruch Minke who provided evidence in 1992 that it was an ion channel that opened in response to light stimulation.[6] The TRPL channel was cloned and characterized in 1992 by the research group of Leonard Kelly.[7]

References

  1. ^ Islam MS, ed (January 2011). Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology. 704. Berlin: Springer. pp. 700. ISBN 978-94-007-0264-6. 
  2. ^ a b Cosens DJ, Manning A (1969). "Abnormal electroretinogram from a Drosophila mutant". Nature 224 (5216): 285–287. doi:10.1038/224285a0. PMID 5344615. 
  3. ^ Leung HT, Tseng-Crank J, Kim E, Mahapatra C, Shino S, Zhou Y, An L, Doerge RW, Pak WL. (2008 Jun 26). "DAG lipase activity is necessary for TRP channel regulation in Drosophila photoreceptors". Neuron 6 (58): 884–896. doi:10.1016/j.neuron.2008.05.001. PMC 2459341. PMID 18579079. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2459341. 
  4. ^ Cosens DJ, Manning A (October 1969). "Abnormal electroretinogram from a Drosophila mutant". Nature 224 (5216): 285–287. doi:10.1038/224285a0. PMID 5344615. 
  5. ^ Montell C, Rubin GM (April 1989). "Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction". Neuron 2 (4): 1313–23. doi:10.1016/0896-6273(89)90069-X. PMID 2516726. 
  6. ^ Hardie RC, Minke B (April 1992). "The trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors". Neuron 8 (4): 643–51. doi:10.1016/0896-6273(92)90086-S. PMID 1314617. 
  7. ^ Phillips AM, Bull A, Kelly LE (April 1992). "Identification of a Drosophila gene encoding a calmodulin-binding protein with homology to the trp phototransduction gene". Neuron 8 (4): 631–42. doi:10.1016/0896-6273(92)90085-R. PMID 1314616. 

External links