Disease relevance of trpl

• Pretreatment of S2-DM1-TRPL cells with 10 microM atropine abolished Gd(3+)-insensitive Ca2+ influx triggered by carbamylcholine, but the response was not blocked by prior incubation with pertussis toxin [1].
• Hormonal stimulations of calcium influx (detected by fura-2) and of an outwardly rectifying current were observed in Sf9 cells coinfected with baculoviruses encoding trpl and various heptahelical receptors for histamine, thrombin, and thromboxane A2, all known to cause phospholipase C-beta activation in mammalian cells [2].
• Expression of Drosophila Ca2+ permeable transient receptor potential-like channel protein in a prostate cancer cell line decreases cell survival [3].
• Using recombinant adenoviruses, expression of the TRPL protein was associated with an increase in both the initial and sustained rates of Ca(2+) inflow [3].
• The effects of expression of Drosophila melanoga ster Ca(2+) permeable transient receptor potential-like (TRPL) channels, under the control of the cytomegalovirus (CMV) or prostate cell-specific promoters, on cell survival and apoptosis in the androgen-sensitive LNCaP prostate cancer cell line were investigated [3].

High impact information on trpl

• We propose that the light-activated current in photoreceptor cells is produced by a combination of TRP homo- and TRP-TRPL heteromultimers [4].
• We show that TRPgamma is highly enriched in photoreceptor cells and preferentially heteromultimerizes with TRPL in vitro and in vivo [5].
• To explain the residual photoresponse that remains in the trp mutant, a third TRP-related subunit has previously been proposed to function with TRPL [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].
• The trpl protein contains two possible calmodulin-binding sites, six transmembrane regions, and a sequence homologous to an ankyrin-like repeat [7].

Chemical compound and disease context of trpl

• 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 [8].
• Consistent with this hypothesis, we recently showed that recombinant Trpl forms Ca(2+)- and Ba(2+)-permeable non-selective cation channels when expressed in Sf9 cells using the baculovirus expression vector [9].

Biological context of trpl

• A previous report indicated that a null trpl mutant does not display any mutant phenotype [10].
• Rescue of trpl(302) with a trpl transgene under heat-shock control resulted in a stimulated fluid transport phenotype that was indistinguishable from wild-type tubules [11].
• Western blotting of tubule preparations from trp and trpl mutants revealed a correlation between TRPL levels and CAP(2b)-stimulated fluid transport and calcium signaling [11].
• Although the identity of the G-proteins and of possible second messengers involved need to be clarified, it is clear that trpl represents a receptor/G-protein regulated cation channel [2].
• In Drosophila photoreceptors, TRP-like (TRPL) channels are localized to the signaling compartment, the rhabdomere, in the dark, and undergo light-induced translocation into the cell body as a mechanism for long-term light-adaptation [12].

Anatomical context of trpl

• Here, the properties of trpl photoreceptor responses were studied by using electroretinogram (ERG) and intracellular recording techniques in combination with light stimuli of relatively long durations [10].
• Likewise, purified recombinant dFKBP59 produced a graded inhibition of TRPL single channel activity in excised inside-out patches when added to the cytoplasmic membrane surface [13].
• Transient receptor potential-like channels are essential for calcium signaling and fluid transport in a Drosophila epithelium [11].
• Thapsigargin and receptor-mediated activation of Drosophila TRPL channels stably expressed in a Drosophila S2 cell line [1].
• The addition of extracellular Ca2+ ([Ca2+]0) to oocytes injected with trpl cRNA and to mock-injected controls, both loaded with the fluorescent Ca2+ indicator fluo-3, induced a rapid initial and a slower sustained rate of increase in fluorescence, which were designated the initial and sustained rates of Ca2+ inflow respectively [14].

Associations of trpl with chemical compounds

• For a wide range of cations, ionic permeability ratios in wild type were always intermediate between those of trp and trpl mutants [15].
• (1997) proposed that Ca(2+) ions entering through the TRP channel modulate TRP and TRPL channel activities differentially [10].
• In some cells, TRPL channels activated by thapsigargin could further be activated by carbamylcholine [1].
• We have stably co-expressed Drosophila TRPL with a Drosophila muscarinic acetylcholine receptor (DM1) in a Drosophila cell line (S2 cells) [1].
• In Drosophila photoreceptors, activation of TRP and TRPL is mediated via the phosphoinositide cascade, with both Ca(2+) and diacylglycerol (DAG) essential for generating the light response [16].

Physical interactions of trpl

• Immunoprecipitations from Sf9 cell lysates using recombinant tagged dFKBP59 and TRPL showed that these proteins directly interact with each other and with INAD [13].
• Identification and characterization of two distinct calmodulin-binding sites in the Trpl ion-channel protein of Drosophila melanogaster [17].

Regulatory relationships of trpl

• In particular, InsP3 infusion, modulation of protein kinase C activity or elevation of intracellular calcium concentration failed to induce trpl currents [18].
• Two phospholipase C inhibitors (U-73122 4 microM and bromo-phenacyl bromide 50 microM) reduced both spontaneous and agonist-induced TRPL activity in S2 cells [19].
• The cDNA encoding the Trpl protein was initially isolated on the basis that the expressed protein binds calmodulin [17].
• The open channel block by Ca(2+) that we characterized is a useful mechanism to improve the signal to noise ratio of the response to intense light when virtually all the large conductance TRPL channels are blocked and only the low conductance TRP channels with lower Ca(2+) affinity are active [20].
• In oocytes incubated in the presence of PMA (to suppress Ca2+ inflow through endogenous receptor-activated Ca2+ channels), the InsP3-induced stimulation of Ca2+ inflow through TRPL channels was more clearly evident than in oocytes incubated in the absence of PMA [21].

Other interactions of trpl

• The Drosophila light-activated conductance is composed of the two channels TRP and TRPL [22].
• Immunoprecipitations from Drosophila S2 cells and from fly head lysates demonstrated that dFKBP59, but not dFKBP12, interacts with TRPL in vivo [13].
• These results provide strong support for the hypothesis that immunophilin dFKBP59 is part of the TRPL-INAD signaling complex and plays an important role in modulation of channel activity via interaction with conserved leucyl-prolyl dipeptides located near the cytoplasmic mouth of the channel [13].
• Finally, we show that arrestin2 is required for the rhabdomeric localization and stability of TRPL channels [12].
• Activation of heterologously expressed Drosophila TRPL channels: Ca2+ is not required and InsP3 is not sufficient [19].

Analytical, diagnostic and therapeutic context of trpl

• Addition of FK506 prior to immunoprecipitation resulted in a temperature-dependent dissociation of dFKBP59 and TRPL [13].
• Site-directed mutagenesis showed that mutations of P702Q or P709Q in the highly conserved TRPL sequence (701)LPPPFNVLP(709) eliminated interaction of the TRPL with dFKBP59 [13].
• Simultaneous whole-cell recordings and ratiometric Indo-1 Ca2+ measurements indicated that agonist (CCh)-induced activation of TRPL channels was not always associated with a rise in Ca2+ [19].
• A low concentration of exogenous calmodulin (introduced by microinjection) activated, and a higher concentration inhibited, the trpl cRNA-induced increase in basal rate of Ca2+ inflow [14].
• Immunofluorescence studies indicated that the expressed TRPL, TRPL (W713G) and TRPL (W814G) proteins are located at the plasma membrane [21].

References