TRPM1 Antibodies

Transient receptor potential cation channel subfamily M member 1 (TRPM1)

Cation channel essential for the depolarizing photoresponse of retinal ON bipolar cells. It's part of the GRM6 signaling cascade.

May play a role in metastasis suppression (By similarity). May act as a spontaneously active, calcium-permeable plasma membrane channel.

Gene Information

Human
Gene Name:	TRPM1
Uniprot:	Q7Z4N2
Entrez:	4308

Family

Belongs to:
transient receptor (TC 1.A.4) family

Alternative Names

CSNB1C; Long transient receptor potential channel 1; LTrpC1; LTRPC1transient receptor potential cation channel subfamily M member 1; melastatin 1; melastatin-1; MLSN; MLSN1transient receptor potential melastatin family; transient receptor potential cation channel, subfamily M, member 1

Molecular Weight

Mass (kDA):
182.178 kDA

Genomic Context

Human
Location:	15q13.3
Sequence:	15; NC_000015.10 (31001061..31161273, complement)

Tissue Specificity

Expressed in the retina where it localizes to the outer plexiform layer. Highly expressed in benign melanocytic nevi and diffusely expressed in various in situ melanomas, but not detected in melanoma metastases. Also expressed in melanocytes and pigmented metastatic melanoma cell lines. In melanocytes expression appears to be regulated at the level of transcription and mRNA processing.

Subcellular Localizations

Cell membrane; Multi-pass membrane protein.

Diseases

• Melanoma
• Night Blindness
• Blind Vision
• Neoplasms
• Congenital Stationary Night Blindness
• Neoplasm Metastasis
• Retinal Diseases
• Malignant Neoplasms
• Skin Neoplasms
• Cutaneous Melanoma
• Melanocytic Nevus
• Horse Diseases

• Myopia
• Metastatic Melanoma
• Malignant Paraganglionic Neoplasm
• Melanoma-associated Retinopathy
• Cell Invasion
• Malignant Neoplasm Of Prostate
• Genetic Diseases, X-linked

Pathways

• Localization
• Cell Death
• Pigmentation
• Pathogenesis
• Cell Proliferation
• Signal Transmission
• Reverse Transcription
• Synaptic Transmission
• Regulation Of Cell Proliferation
• Transport
• Cell Adhesion
• Immune Response
• Chemotaxis

• System Development
• Translation
• Cell Differentiation
• Mrna Processing
• Regulation Of Growth
• Melanocyte Differentiation
• Thymus Development

PTMs

• Cleavage

• Sumoylation

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/TRPM1

Best Uses Of The TRPM1 Marker

This article will focus on Steven Boster’s discovery about TRPM1’s localization on rod ON Bipolar Cell Dendrites and its possible clinical uses. We will also discuss TRPM1’s genetics as well as its clinical applications. After reading this article, you will be equipped with all the information necessary to make a decision about this new marker. The end goal is to maximize the usefulness of this new tool in research.

TRPM1 localization on rod ON bipolar cell dendrites

This article discusses the functional property of TRPM1, an transient potassium channel found on the dendrites and rod ON bipolar cellular cells. We hypothesize that Gbg, a subunit of the GluR6 family, may play a role in the closure and trafficking of TRPM1. Other components could also be involved in the TRPM1's open conformation.

A confocal microscopic image of the macaque eye shows the immunofluorescence for TRPM1 in rod bipolar cells. The cells were stained with an anti-PKCAa antibody, which is associated to phosphorylation. The Nomarski image for the same section is shown blue. Other abbreviations for the Nomarski image of the same section include the outer and inner plexiform layers, inner nuclear layers, and ganglion-cell layer.

The mutant shows a hyperbolic profile for the BRET signal when paired with Gbg. It reaches its maximum at a ratio of acceptor/donor of approximately 1. The mutant protein that carries the C-terminus (TRPM1) interacted with its N-terminus showed a weaker signal. These experiments show that TRPM1 is localized in rod ON bipolar cells by Gbg.

We also observed a decrease TRPM1 in mice deficient in Lrit3nob6. These mice also lacked Gb5 and the mGluR6 required for cone ON bipolar cellular dendrite formation. This suggests that LRIT3 may be involved in cone synapse formation in these mice. This is an exciting and new discovery!

These results suggest that TRPM1 can play a role in bipolar cell function by controlling mGluR6's activity. The mGluR6 mabotropic gaomate receptor activates the heterotrimeric Gaob3g13 and closes the TRPM1 canal. The original theory suggested that TRPM1 is a constitutively open channel. This has been shown to be incorrect. The mutant Gao shut down the TRPM1 channels of rd10 mice by using reagents to alter the activity Gbg and Gao. Wild-type Gao did this without any problems.

Clinical applications

TRPM1 is a gene that encodes a protein which is expressed in melanocytes. This protein may help with melanogenesis and calcium homeostasis. Its expression might be a promising therapeutic target in the treatment for pigmentation disorders. The TRPM1 marker is expressed in melanocytes in dark and light-pigmented skin. The mRNA levels of TRPM1 in human epidermal melanocytes correlate with melanin content. Levels of TRPM1 have a higher level in dark-pigmented than light-pigmented. It also appears that the two splice variants of the TRPM1 gene are distinct.

TRPM1 is found to be localized on rod ON bipolar cell lines, similar to the marker Nyctalopin8. These findings suggest that TRPM1 might be associated with the somata in bipolar cells. This suggests that it is likely to be regulated by mGluR6. The TRPM1 cation channel is mGluR6-coupled and is associated with ON bipolar cells.

The TRPM1 gene expression was linked to the diagnosis of Spitz nevus or nodular malignant melanoma. Traditional factors, such as tumor size, were not associated to TRPM1 expression. It was interesting to note that the decrease in TRPM1 expression was associated with an increase in patient age in Spitz-nevi. Reduced TRPM1 expression was associated in nodular melanomas with mitoses or ulceration.

TRPM1 is involved with photoreceptor growth and the JAKSTAT cascade. This gene also regulates ROS. Moreover, it is involved in regulating the apoptosis of cells and inhibits their growth. These results show that TRPM1 plays a significant role in photoreceptor function. Clinical applications of the TRPM1 marker in this context are rapidly emerging.

Genetics

This study looked at the frequency of TRPM1 exons 2-4 in Ashkenazi Jews with Lithuanian and Russian heritage. This study revealed that the deletion is heterozygous (2.75% in Ashkenazi subjects) and homozygous (1.22% in Sephardic). Myopia and CSNB are most common due to the exon 2-7 deletion. It is associated with a high-risk variant frequency.

To test this gene, DNA extracted from peripheral blood was used. Qiagen produced the Gentra Puregene Blood Kit that isolated genomic DNA. The genomic DNA was sequenced with a CSNB panel that also included the CABP4 gene and the CACNA1F genes, as well as the GRM6 and the SAG genes. The gene sequences were aligned with the reference genome to determine the presence of a specific SNP.

Additionally, the TRPM1 enhancer region is highly conserved both in mouse and human cells. This conservation includes high spacing between Eboxes within species. This promoter area is required by MITF in order to have melanocytes transcriptional activity. This study suggests that TRPM1 is involved in melanin production. This association may also be due to a different mechanism.

In human primary melanocytes infected by AdV–control, AdV–MITF and AdV–MITF(DN), viruses, MITF regulated the expression of TRPM1 (and MITF) and MITF. Both markers were detected in melanocytes and normalized against endogenous b-actin at each time point. It is important to understand the role played by MITF in regulating TRPM1 transcription.

Molecular biology

The TRPM1 gene belongs to the subfamily of calcium channels, which comprises structurally and functionally diverse members. The genes have a TRPbox at their C-termini, but no TRPV repeats or ankyrins. The protein also shares an extensive TRPM homology domain. This domain plays important roles in the regulation and development of cell physiology. The TRPM1 gene has been widely used in cancer research including studies on lung function and human airway.

There are many places where the TRPM1 gene can be found in the genome. The coding region, which is the most common area of the gene, is used for determining the evolutionary distance between an individual and the cladogram. Fitch Margoliash measures genetic distances. This algorithm is used for constructing phylogenetic tree based on genetic distance data. The TRPM1 gene contains two coding exons.

TRPM1 can be used in many areas of biology, including cancer research. Its potential therapeutic use in melanoma is one example. TRPM8 is a resistance gene in melanoma cells that are resistant to chemotherapy or other treatments. However, the role of TRPM8 in cancer development is not fully understood. It is important to remember that TRPM8 expression can vary by melanoma types, and TRPM8 levels may correlate with the aggressiveness or severity of the tumors.

TRP protein marker markers from other TRPs may be useful in cell or gene therapy research. TRPM1 could increase intracellular Ca2+ concentrations within tumor cells and other cancerous cells. TRPM2 can be found in brain, bone marrow and brain. TRPV, TRPM2 and the TRP protein receptors TRPV share a pore region. This may be important for their gating.