Phylogenetic analysis and expression of zebrafish transient receptor potential melastatin family genes.

BACKGROUND: The transient receptor potential melastatin (TRPM) gene family belongs to the superfamily of nonselective TRP ion channels. TRP channels are cellular sensors, detecting a multitude of inputs, including temperature, light, chemical, and mechanical stimuli. Recent studies revealed diverse roles during development, linking TRP channels to differentiation, proliferation, cell motility, cell death, and survival. A detailed description of this gene family in the zebrafish is still missing. RESULTS: Phylogenetic analysis revealed 11 trpm genes in the zebrafish genome. The zebrafish orthologs of mammalian TRPM1 and TRPM4 are duplicated and quadruplicated, respectively, and TRPM8, a cold sensitive channel has been lost in zebrafish. Whole-mount in situ hybridization experiments revealed dynamic expression pattern of trpm genes in the developing embryo and early larva. Transcripts were mainly found in neural cell clusters, but also in tissues involved in ion homeostasis. CONCLUSIONS: Our results suggest a role of TRPM channels in sensory information processing, including vision, olfaction, taste, and mechanosensation. An involvement in developmental processes is likely, as some trpm genes were found to be expressed in differentiating cells. Our data now provide a basis for functional analyses of this gene family of ion channels in the vertebrate model organism Danio rerio.

Vanilloid and melastatin transient receptor potential channels in vascular smooth muscle.

The mammalian transient receptor potential (TRP) superfamily consists of six subfamilies that are defined by structural homology: TRPC (conventional or canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPP (polycystin), and TRPML (mucoliptin). This review focuses on channels belonging to the vanilloid (V) and melastatin (M) TRP subfamilies. The TRPV subfamily consists of six members (TRPV1-6) and the TRPM subfamily has eight (TRPM1-8). The basic biophysical properties of these channels are briefly described. All of these channels except TRPV5, TRPV6, and TRPM1 are reportedly present in arterial smooth muscle from various segments of the vasculature. Studies demonstrating involvement of TRPV1, TRPV2, TRPV4, TRPM4, TRPM7, and TRPM8 in regulation of arterial smooth muscle function are reviewed. The functions of TRPV3, TRPM2, TRPM3, and TRPM6 channels in arterial myocytes have not been reported.

Dynamic expression of the TRPM subgroup of ion channels in developing mouse sensory neurons.

Despite the significance of transient receptor potential (TRP) channels in sensory physiology, little is known of the expression and developmental regulation of the TRPM (melastatin) subgroup in sensory neurons. In order to find out if the eight TRPM subgroup members (TRPM1-TRPM8) have a possible role in the sensory nervous system, we characterized the developmental regulation of their expression in mouse dorsal root ganglion (DRG) from embryonic (E) day 12 to adulthood. Transcripts for all channels except for TRPM1 were detected in lumbar and thoracic DRG and in nodose ganglion (NG) with distinguishable expression patterns from E12 until adult. For most channels, the expression increased from E14 to adult with the exception of TRPM5, which displayed transient high levels during embryonic and early postnatal stages. Cellular localization of TRPM8 mRNA was found only in a limited subset of very small diameter neurons distinct in size from other populations. These neurons did not bind isolectin B4 (IB4) and expressed neither the neuropeptide calcitonin gene-related peptide (CGRP) nor neurofilament (NF)200. This suggests that TRPM8(+) thermoreceptive sensory neurons fall into a separate group of very small sized neurons distinct from peptidergic and IB4(+) subtypes of sensory neurons. Our results, showing the expression and dynamic regulation of TRPM channels during development, indicate that many TRPM subfamily members could participate during nervous system development and in the adult by determining distinct physiological properties of sensory neurons.

X-ray crystal structure of a TRPM assembly domain reveals an antiparallel four-stranded coiled-coil.

Transient receptor potential (TRP) channels comprise a large family of tetrameric cation-selective ion channels that respond to diverse forms of sensory input. Earlier studies showed that members of the TRPM subclass possess a self-assembling tetrameric C-terminal cytoplasmic coiled-coil domain that underlies channel assembly and trafficking. Here, we present the high-resolution crystal structure of the coiled-coil domain of the channel enzyme TRPM7. The crystal structure, together with biochemical experiments, reveals an unexpected four-stranded antiparallel coiled-coil architecture that bears unique features relative to other antiparallel coiled-coils. Structural analysis indicates that a limited set of interactions encode assembly specificity determinants and uncovers a previously unnoticed segregation of TRPM assembly domains into two families that correspond with the phylogenetic divisions seen for the complete subunits. Together, the data provide a framework for understanding the mechanism of TRPM channel assembly and highlight the diversity of forms found in the coiled-coil fold.

Transient receptor potential (TRP) cation channels: rewarding unique proteins.

The discovery of the Transient Receptor Potential (TRP) superfamily of versatile and polymodal cation channels has dramatically extended our molecular understanding of cellular sensors. The main surprising properties are their diversity in ion selectivity and the polymodal mechanisms of activation, which necessarily result in equally diverse cell functions. They are involved in sensory functions, e.g. the perception of temperature, smell, taste, pain, mechanical signals and respond to many natural compounds used in "traditional medicine". TRP channels are main players in Ca2+ signalling, which controls a plethora of events ranging from neurotransmitter release to gene transcription and cell death. They are also involved in homeostatic functions, e.g. epithelial Ca2+ and Mg2+ reabsorption and lysosomal pH regulation. TRP channel dysfunction contributes to certain human diseases. Finally, TRP channels will become important novel pharmacological targets for the treatment of human diseases and for modulation of sensory functions, e.g. the perception of flavor.

Tissue distribution profiles of the human TRPM cation channel family.

Eight members of the TRP-melastatin (TRPM) subfamily have been identified, whose physiological functions and distribution are poorly characterized. Although tissue expression and distribution patterns have been reported for individual TRPM channels, comparisons between individual studies are not possible because of variations in analysis techniques and tissue selection. 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). These techniques generated comparative distribution profiles and demonstrated tissue-specific co-expression of TRPM mRNA species, indicating significant potential for the formation of heteromeric channels. TRPM channels 2, 4, 5, 6, and 7 in contrast to 1, 3, and 8 are widely distributed in the CNS and periphery. The tissues demonstrating highest expression for individual family members were brain (TRPM1), brain and bone marrow (TRPM2), brain and pituitary (TRPM3), intestine and prostate (TRPM4), intestine, pancreas, and prostate (TRPM5), intestine and brain (TRPM6), heart, pituitary, bone, and adipose tissue (TRPM7), and prostate and liver (TRPM8). The data reported here will guide the elucidation of TRPM channel physiological functions.