Disease relevance of trp

• Null mutations in trp cause impairment of visual transduction, mislocalization of INAD, and retinal degeneration [1].
• Furthermore, mutations in several members of TRP-related channel proteins are responsible for several diseases, such as several tumors and neurodegenerative disorders [2].
• 4. Knowledge that TRP channels are relevant to vascular smooth muscle cells in both their contractile and proliferative phenotypes should pave the way for a better understanding of vascular biology and provide the basis for the discovery of a new set of therapeutic agents targeted to vascular disease [3].

High impact information on trp

• TRP channel proteins and signal transduction [2].
• TRP-related channel proteins are found in a variety of organisms, tissues, and cell types, including nonexcitable, smooth muscle, and neuronal cells [2].
• The molecular domains that are conserved in all members of the TRP family constitute parts of the transmembrane domains and in most members also the ankyrin-like repeats at the NH2 terminal of the protein and a "TRP domain" at the COOH terminal, which is a highly conserved 25-amino acid stretch with still unknown function [2].
• We propose that the light-activated current in photoreceptor cells is produced by a combination of TRP homo- and TRP-TRPL heteromultimers [4].
• Contrary to current models of excitation and TRP channel function, we demonstrate that the transient phenotype of trp mutants can be explained by CAM regulation of the TRPL channel rather than by the loss of a store-operated conductance leading to depletion of the internal stores [5].

Chemical compound and disease context of trp

• This retinal degeneration was greatly suppressed by elimination of the Na(+)/Ca(2+) exchanger, CalX, indicating that the cell death was due primarily to deficient Ca(2+) entry rather than disruption of the TRP-anchoring function [1].

Biological context of trp

• 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 [6].
• Thus, PLC and its downstream second messengers, Ca(2+) and DAG, constitute critical mediators of TRP/TRPL gating in vivo [7].
• Phenotypes of trpl mutants and interactions between the transient receptor potential (TRP) and TRP-like channels in Drosophila [8].
• Wild-type immunocomplexes incubated with [(32)P]ATP revealed phosphorylation of TRP and INAD [9].
• In Drosophila phototransduction the cation channels TRP and TRP-like (TRPL) are the targets of a prototypical G protein-coupled signaling pathway [10].

Anatomical context of trp

• Abolishing Ca2+ influx in wild-type photoreceptors mimicked inactivation, while raising Ca2+ by blocking Na+/Ca2+ exchange prevented inactivation in trp [11].
• It is not clear how the Ca2+ store depletion signal is relayed to the plasma membrane and whether both TRP and TRPL participate in this process [12].
• Coexpression of Drosophila TRP and TRP-like proteins in Xenopus oocytes reconstitutes capacitative Ca2+ entry [12].
• Transient receptor potential (TRP) channels across species are expressed in sensory receptor cells, and often localized to specialized subcellular sites [13].
• At least seven proteins bind INAD, including the transient receptor potential (TRP) channel, which depends on INAD for localization to the phototransducing organelle, the rhabdomere [14].

Associations of trp with chemical compounds

• Calcium influx via TRP channels is required to maintain PIP2 levels in Drosophila photoreceptors [11].
• 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 [7].
• ATP depletion or inhibition of protein kinase C activated the TRP channels, while photo-release of caged ATP or application of phorbol ester antagonized channels openings in the dark [15].
• Furthermore, Mg(2+)-dependent stable phosphorylation event by ATPgammaS or protein phosphatase inhibition by calyculin A abolished activation of the TRP and TRPL channels [15].
• Recent evidence is reviewed suggesting that Drosophila TRP channels are activated by one or more lipid products of PLC activity: namely diacylglycerol (DAG), its metabolites (polyunsaturated fatty acids) or the reduction in phosphatidylinositol 4,5-bisphosphate (PIP(2)) [16].

Physical interactions of trp

• We report that anti-INAD antibodies coimmunoprecipitate TRP, identified by its electrophoretic mobility, cross reactivity with anti-TRP antibody, and absence in a null allele trp mutant [17].
• Furthermore, Rab11 is required for transport of TRP, another rhabdomeric protein, and for development of specialized membrane structures within Garland cells [18].

Enzymatic interactions of trp

• We reveal that Ser982 of TRP is phosphorylated by eye-PKC in vitro and, importantly, in the fly eye, as shown by mass spectrometry [19].

Regulatory relationships of trp

• These results suggest that the INAD macromolecular complex plays an essential role in termination of the light response by promoting efficient phosphorylation at Ser982 of TRP for fast deactivation of the visual signaling [19].
• 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].
• Mutations in calnexin also impair the ability of photoreceptor cells to control cytosolic Ca2+ levels following activation of the light-sensitive TRP channels [21].

Other interactions of trp

• The Drosophila light-activated conductance is composed of the two channels TRP and TRPL [22].
• 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 [6].
• Moreover, deactivation is regulated by the interaction between INAD and TRP, because abrogation of this interaction in InaD(p215) results in slow deactivation similar to that of inaC(p209) lacking eye-PKC [19].
• Together our results demonstrate the contribution of PI depletion to the rdgA phenotype and provide evidence that depletion of PI and its metabolites might be a key signal for TRP channel activation in vivo [23].
• Here, we report on the Drosophila inaF gene, which encodes a highly eye-enriched protein, INAF, that appears to be required for TRP channel function [24].

Analytical, diagnostic and therapeutic context of trp

• Whole-cell recordings revealed that light-sensitive Ca2+ channels encoded by the trp gene were constitutively active in rdgA photoreceptors [25].
• RT-PCR revealed expression of trp, trpl, and trpgamma in tubules [6].
• In the present study we applied patch-clamp whole-cell recordings and measurements of Ca(2+) concentration by ion-selective microelectrodes in eyes of normal and mutant Drosophila to isolate the TRP and TRP-like (TRPL)-dependent currents [26].
• The light-driven pupil mechanism, consisting of an assembly of mobile pigment granules inside the photoreceptor cells, has been investigated by in vivo reflection microspectrophotometry in wild type (WT) Drosophila and in the photoreceptor mutants inaC and trp [27].
• As revealed by partial cDNA sequence analysis, three of these genes represent the Calliphora homologs of Drosophila trp, inaC and InaD, while the other two displayed no homology to known genes [28].

References