Disease relevance of trpgamma

• To test this hypothesis, the effect of thapsigargin, a selective inhibitor of the endoplasmic reticulum Ca2+ pump, on trp- and trpl-induced whole cell membrane current was determined using the baculovirus Sf9 insect cell expression system [1].

High impact information on trpgamma

• Studies on visual signal transduction in Drosophila led to the hypothesis that a protein encoded in trp may be a component of CCE channels [2].
• As well as being a major charge carrier for the light-induced current, Ca2+ influx via the trp-dependent channels appears to be required for refilling Ca2+ stores sensitive to inositol 1,4,5-trisphosphate and for feedback regulation (light adaptation) of the transduction cascade [3].
• Using genetically targeted PIP2-sensitive inward rectifier channels (Kir2.1) as biosensors, we provide evidence that trp decay reflects depletion of PIP2 [4].
• We show that TRPgamma is highly enriched in photoreceptor cells and preferentially heteromultimerizes with TRPL in vitro and in vivo [5].
• The TIM response to a light pulse was attenuated in flies that were mutant for the transient receptor potential (trp) and trp-like (trpl) genes, which are required for calcium conductance in the visual transduction cascade [6].

Biological context of trpgamma

• Despite the prevalence of store-operated Ca2+ entry, no vertebrate channel responsible for store-operated Ca2+ entry has been reported. trp (transient receptor potential), a Drosophila gene required in phototransduction, encodes the only known candidate for such a channel throughout phylogeny [7].
• Identification of common binding sites for calmodulin and inositol 1,4,5-trisphosphate receptors on the carboxyl termini of trp channels [8].
• Comparison of the amino acid sequence encoded by this cDNA with entries in the OWL composite protein sequence database reveals greatest sequence similarity with the products of the Drosophila trp and trpl genes [9].
• Measurement of cytosolic calcium concentrations ([Ca(2+)](i)) in tubule principal cells using an aequorin transgene in trp and trpl mutants showed a reduction in calcium responses in trpl(302) [10].
• The identification of a protein similar to the trp gene product, yet also able to bind Ca2+/calmodulin, allows for a reinterpretation of the phenotype of the trp mutations and suggests that both genes may encode light-sensitive ion channels [11].

Anatomical context of trpgamma

• Furthermore, several lines of evidence suggest that the trp gene product TRP is a candidate subunit of the plasma membrane channel that is activated by Ca2+ store depletion [12].
• Northern blot analysis confirmed that trp, inaC and InaD transcripts were present in RNA isolated from the retina, but not in RNA isolated from brain or thorax [13].
• It is thus possible that capacitative calcium entry in Xenopus oocytes is mediated by a homologue of trp [14].

Associations of trpgamma with chemical compounds

• RT-PCR revealed expression of trp, trpl, and trpgamma in tubules [10].
• In Calcium Green-5N-loaded trp mutants, which lack a large fraction of the Ca2+ permeability underlying the light-evoked inward current, the Ca2+ signal was smaller relative to wild-type photoreceptors [15].
• A unique proline-rich region in the COOH-terminal tail of trp, which is absent in trpl, may be necessary for capacitative Ca2+ entry [1].
• Drosophila photoreceptors express two putative cation channels encoded by the transient receptor potential (trp) and trp-like (trpl) genes, which represent prototypical members of a novel family of phosphoinositide-regulated calcium influx channels [16].
• By contrast, in trp photoreceptors, which lack one class of Ca2+ permeable light-sensitive channel, photolysis of DM-nitrophen induced a significant facilitation during the falling phase of the response, but during the rising phase photolysis significantly depressed the overall response [17].
• The most potent activator of TRPgamma, the stable analogue of arachidonic acid, 5,8,11,14-eicosatetraynoic acid, induced currents in single channel recordings [18].

Other interactions of trpgamma

• Use of antipeptide polyclonal antibodies for TRP, TRPL, and TRPgamma showed expression of all three channels in type 1 (principal) cells in the tubule main segment [10].

Analytical, diagnostic and therapeutic context of trpgamma

• Molecular cloning of a widely expressed human homologue for the Drosophila trp gene [19].
• Western blot analyses revealed that trp, inaC and InaD protein are specifically associated with the rhabdomeral photoreceptor membrane [13].

References