Trpm3

Abstract

Like most other members of the TRP family, the Trpm3 gene encodes proteins that form cation-permeable ion channels on the plasma membrane. However, TRPM3 proteins have several unique features that set them apart from the other members of this diverse family. The Trpm3 gene encodes for a surprisingly large number of isoforms generated mainly by alternative splicing. Only for two of the (at least) eight sites at which sequence diversity is generated the functional consequences have been elucidated, one leading to nonfunctional channels, the other one profoundly affecting the ionic selectivity. In the Trpm3 gene an intronic microRNA (miR-204) is co-transcribed with Trpm3. By regulating the expression of a multitude of genes, miR-204 increases the functional complexity of the Trpm3 locus. Over the past years, important progress has been made in discovering pharmacological tools to manipulate TRPM3 channel activity. These substances have facilitated the identification of endogenously expressed functional TRPM3 channels in nociceptive neurons, pancreatic beta cells, and vascular smooth muscle cells, among others. TRPM3 channels, which themselves are temperature sensitive, thus have been implicated in sensing noxious heat, in modulating insulin release, and in secretion of inflammatory cytokines. However, in many tissues where TRPM3 proteins are known to be expressed, no functional role has been identified for these channels so far. Because of the availability of adequate pharmacological and genetic tools, it is expected that future investigations on TRPM3 channels will unravel important new aspects and functions of these channels.

TRPM3 and miR-204 Establish a Regulatory Circuit that Controls Oncogenic Autophagy in Clear Cell Renal Cell Carcinoma

“…MiR-204 is expressed from intron 6 of the gene encoding a transient receptor potential non-selective cation channel, subfamily M, member 3, TRPM3, that conducts Ca 2+ and Zn 2+ ions (Harteneck, 2005, Oberwinkel and Phillipp, 2007, Wagner et al, 2010). Both, TRPM3 and miR-204 show enriched expression in human kidney (Grimm et al, 2003).…”

VHL-Regulated MiR-204 Suppresses Tumor Growth through Inhibition of LC3B-Mediated Autophagy in Renal Clear Cell Carcinoma

“…Conversely, the use of antagomirs may allow for a decrease in the level and activity of miRs that promote oncogenesis (Krutzfeldt et al, 2005). MiR-204 is expressed from the large intron 6 of TRPM3 , which is located on chromosome 9q21.12 and encodes a transient receptor potential, Ca 2+ -permeable, non-selective cation channel (Oberwinkler & Phillipp, 2007) (Figure 1A). Both miR-204 and TRPM3 are expressed at higher levels in human kidney as compared with other organ tested (Lu et al, 2005).…”

Activation of TRPM3 by a potent synthetic ligand reveals a role in peptide release

“…In addition, TRPM3 is expressed in pancreatic beta cells, where it is involved in controlling insulin release (4), as well as in various tissues, including brain, pituitary gland, eye, kidney, and adipose tissue (reviewed in ref. 9). …”