Disease relevance of TRPM1

• In addition, MITF and TRPM1 mRNA levels were correlated tightly across a series of human melanoma cell lines [1].
• Down-regulation of MLSN1 expression in human cutaneous melanoma, as indicated by in situ hybridization, appears to be a prognostic marker for melanoma metastasis [2].
• Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family [3].

Psychiatry related information on TRPM1

• Finally, we discuss the possibility that TRPM channels may provide therapeutic targets for degenerative diseases involving oxidative stress-related pathologies including diabetes and Alzheimer's disease [4].

High impact information on TRPM1

• In Caenorhabditis elegans, the melastatin-type transient receptor potential (TRPM) channel, especially TRPM7, was suggested as being involved in defecation rhythm [5].
• TRPM5, a member of the TRPM subfamily, plays an important role in taste receptors, although its activation mechanism remains controversial and its function in signal transduction is unknown [6].
• Here, we describe the identification and characterization of an additional TRPM protein TRPM4 [7].
• The highest homologies are observed with the human TRPC7 and with melastatin 1 ( MLSN1 ), whose transcript is downregulated in metastatic melanomas [8].
• Identification and characterization of MTR1, a novel gene with homology to melastatin (MLSN1) and the trp gene family located in the BWS-WT2 critical region on chromosome 11p15.5 and showing allele-specific expression [8].

Chemical compound and disease context of TRPM1

• Treatment of pigmented melanoma cells with the differentiation-inducing agent, HMBA, results in up-regulation of the 5.4-kb MLSN1 mRNA as well as short RNAs [9].

Biological context of TRPM1

• Endogenous TRPM1 expression responded strongly to MITF up- or down-regulation, as did TRPM1 promoter-driven reporters [1].
• Mutagenesis reducing the number of MITF binding sites in the promoter of TRPM1 from three to one eliminated the difference in transcriptional activity between the MITF mutants [10].
• Although we currently lack animal models allowing a detailed assessment of the potential involvement of TRPM family members in modulating the immune response, the powerful combination of molecular and cellular biology, biochemistry, and electrophysiology have provided the first clues as to how these molecules could contribute to immunity [11].
• Western blot analysis using polyclonal rabbit anti-human MLSN1 antibodies identified several polypeptides, presumably generated by both alternative splicing of MLSN1 messenger RNA (mRNA) and proteolytic cleavage, in both melanocytes and metastatic melanoma cells [2].
• These findings indicate that TRPM6 is crucial for magnesium homeostasis and implicate a TRPM family member in human disease [3].

Anatomical context of TRPM1

• Transcriptional regulation of the melanoma prognostic marker melastatin (TRPM1) by MITF in melanocytes and melanoma [1].
• We report here a comparative analysis of the expression patterns of all of the human TRPM channels in selected peripheral tissues and the central nervous system (CNS) using two distinct but complimentary approaches: TaqMan and SYBR Green real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) [12].
• Three monoclonal antibodies, designated RM-1, TRPM-1, and TRPM-2, were raised against rat peritoneal macrophages [13].
• RM-1 and TRPM-1 were also reactive with interdigitating cells (IDCs) in the thymus-dependent area and with Langerhans cells in the skin, whereas TRPM-2 failed to demonstrate IDCs in thymic medulla and Langerhans cells [13].
• RM-1 recognized a cell surface antigen; reaction products for TRPM-1 were found on a part of the cell membrane and in the cytoplasmic vacuoles; and those of TRPM-2 were present along the nuclear envelope and intracytoplasmic vacuoles [13].

Associations of TRPM1 with chemical compounds

• We reveal that TRPM4 and MLSN each mediate Ca(2+) entry when expressed in HEK293 cells [7].
• TRPM proteins, consisting of six putative transmembrane domains and intracellular N and C termini, form monovalent-permeable cation channels with variable selectivity for Ca(2+), Mg(2+) and other divalent cations [14].
• HMBA appears to up-regulate MLSN1 transcripts derived mainly from the 5'-end [9].
• Incorporation of negative charge in place of Gln-981 between the pore helix and selectivity filter by changing it to glutamate, which is present in the more Ca(2+)-permeable TRPM channels, substantially increased Ca(2+) permeability [15].

Regulatory relationships of TRPM1

• This prompted examination of whether MITF also might transcriptionally regulate TRPM1 expression [1].

Other interactions of TRPM1

• Mice homozygously mutated in MITF showed a dramatic decrease in TRPM1 expression [1].
• TRPM2 proteins belong to the melastatin-related transient receptor potential or TRPM subfamily and form Ca(2+)-permeable cationic channels activated by intracellular adenosine diphosphoribose (ADPR) [16].
• TRPM3, a member of the melastatin-like transient receptor potential channel subfamily (TRPM), is predominantly expressed in human kidney and brain [17].
• Among the two other TRP subfamilies, TRPMV and TRPM, at least TRPV4 and TRPM4 are EC channels [18].
• TRPM (transient receptor potential melastatin-like) channels are distinct from many other members of the transient receptor potential family in regard to their overall size (>1000 amino acids), the lack of N-terminal ankyrin-like repeats, and hydrophobicity predictions that may allow for more than six transmembrane regions [19].

Analytical, diagnostic and therapeutic context of TRPM1

• The TRPM1 promoter contains multiple MITF consensus binding elements that were seen by chromatin immunoprecipitation to be occupied by endogenous MITF within melanoma cells [1].
• Northern blot and RT-PCR analyses with DNA probes and oligonucleotide primers that correspond to distinct regions of full-length MLSN1 mRNA indicated that the short transcripts contained sequences corresponding primarily to either 5'- or 3'-end of the 5.4-kb mRNA [9].
• Increasing loss of MLSN mRNA significantly impacted on disease free survival (DFS) by multivariate analysis (58 vs. 0% 2 years DFS, </= 75 vs. >75% mRNA loss, p = 0.02) [20].

References