TRPM1
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Transient receptor potential cation channel subfamily M member 1 is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''TRPM1''
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.


Function

The protein encoded by this gene is a member of the
transient receptor potential Transient receptor potential channels (TRP channels) are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC ( "C" for canonical), TR ...
(TRP) family of non-selective cation channels. It is expressed in the retina, in a subset of
bipolar cells A bipolar neuron, or bipolar cell, is a type of neuron that has two extensions (one axon and one dendrite). Many bipolar cells are specialized sensory neurons for the transmission of sense. As such, they are part of the sensory pathways for smell, ...
termed ON bipolar cells. These cells form
synapse In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses from ...
s with either rods or cones, collecting signals from them. In the dark, the signal arrives in the form of the
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neu ...
glutamate, which is detected by a
G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
(GPCR) signal transduction cascade. Detection of glutamate by the GPCR
Metabotropic glutamate receptor 6 Glutamate receptor, metabotropic 6, also known as GRM6 or mGluR6, is a protein which in humans is encoded by the ''GRM6'' gene. Function L- glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ...
results in closing of the TRPM1 channel. At the onset of light, glutamate release is halted and mGluR6 is deactivated; this results in opening of the TRPM1 channel, influx of sodium and calcium, and
depolarization In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is ess ...
of the bipolar cell. In addition to the retina, TRPM1 is also expressed in
melanocyte Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and hear ...
s, which are melanin-producing cells in the skin. The expression of TRPM1 is inversely correlated with
melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
aggressiveness, suggesting that it might suppress
melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, the ...
. However, subsequent work showed that a
microRNA MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. mi ...
located in an
intron An intron is any Nucleic acid sequence, nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of ...
of the ''TRPM1'' gene, rather than the TRPM1 protein itself, is responsible for the tumor suppressor function. The expression of both TRPM1 and the microRNA are regulated by the
Microphthalmia-associated transcription factor Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the ''MITF'' gene. MITF is a basic helix-loop-helix leucine zipper transcription facto ...
.


Clinical significance

Mutations in TRPM1 are associated with
congenital stationary night blindness Congenital stationary night blindness (CSNB) is a rare non-progressive retinal disorder. People with CSNB often have difficulty adapting to low light situations due to impaired photoreceptor transmission. These patients may also have reduced visua ...
in humans and coat spotting patterns in
Appaloosa The Appaloosa is an American horse breed best known for its colorful spotted coat pattern. There is a wide range of body types within the breed, stemming from the influence of multiple breeds of horses throughout its history. Each horse's colo ...
horses.


See also

* TRPM


References


External links

* Ion channels {{membrane-protein-stub