Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transient receptor potential protein (Trp) is a putative capacitative Ca2+ entry channel present in fly photoreceptors, which use the inositol 1,4,5-trisphosphate (InsP3) signaling pathway for phototransduction. By immunoprecipitation studies, we find that Trp is associated into a multiprotein complex with the norpA-encoded phospholipase C, an eye-specific protein kinase C (InaC) and with the InaD protein (InaD). InaD is a putative substrate of InaC and contains two PDZ repeats, putative protein-protein interaction domains. These proteins are present in the photoreceptor membrane at about equimolar ratios. The Trp homolog analyzed here is isolated together with NorpA, InaC and InaD from blowfly (Calliphora) photoreceptors. Compared to Drosophila Trp, the Calliphora Trp homolog displays 77% amino acid identity. The highest sequence conservation is found in the region that contains the putative transmembrane domains S1-S6 (91% amino acid identity). As investigated by immunogold labeling with specific antibodies directed against Trp and InaD, the Trp signaling complex is located in the microvillar membranes of the photoreceptor cells. The spatial distribution of the signaling complex argues against a direct conformational coupling of Trp to an InsP3 receptor supposed to be present in the membrane of internal photoreceptor Ca2+ stores. It is suggested that the organization of signal transducing proteins into a multiprotein complex provides the structural basis for an efficient and fast activation and regulation of Ca2+ entry through the Trp channel.
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PMID:The transient receptor potential protein (Trp), a putative store-operated Ca2+ channel essential for phosphoinositide-mediated photoreception, forms a signaling complex with NorpA, InaC and InaD. 900 79

This article summarizes the literature on receptor-operated Ca2(+)-permeable nonselective cation channels in vascular smooth muscle cells. One of these conductances, the P2X1 receptor, is a classic ligand-gated channel, but others are likely to be mediated via G-protein-coupled receptors. The most studied receptor-operated channel in vascular myocytes is the norepinephrine-evoked nonselective cation channel in rabbit portal vein myocytes. The data regarding the transduction mechanisms and biophysical properties of whole-cell and single-channel currents in this preparation are described. The channels have a conductance of 20 to 25 pS and complex kinetic behavior with at least two open and two closed states. These channels are activated by norepinephrine and acetylcholine via G-protein-coupled receptors linked to phospholipase C and by diacylglycerol (DAG). The action of DAG occurs by a mechanism independent of protein kinase C, but other kinases may mediate the responses to norepinephrine and DAG. In addition, activation of tyrosine kinases leads to opening of this channel. Other vasoconstrictors, such as endothelin, vasopressin, serotonin, and angiotensin II, open Ca2(+)-permeable nonselective cation channels, but there may be differences between these conductances and the norepinephrine-evoked channels. A homologue of the transient receptor potential protein (TRPC6) is an essential component of the norepinephrine-activated channel in rabbit portal vein, and it is likely that this family of proteins plays an important role in mediating Ca2+ influx in vascular smooth muscle.
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PMID:Receptor-operated Ca2(+)-permeable nonselective cation channels in vascular smooth muscle: a physiologic perspective. 1203 May 34

In the present study, we examined the mechanisms through which erythropoietin (Epo) activates the calcium-permeable transient receptor potential protein channel (TRPC)2. Erythroblasts were isolated from the spleens of phenylhydrazine-treated mice, and Epo stimulation resulted in a significant and dose-dependent increase in intracellular calcium concentration ([Ca(2+)](i)). This increase in [Ca(2+)](i) was inhibited by pretreatment with the phospholipase C (PLC) inhibitor U-73122 but not by the inactive analog U-73343, demonstrating the requirement for PLC activity in Epo-modulated Ca(2+) influx in primary erythroid cells. To determine whether PLC is involved in the activation of TRPC2 by Epo, cell models were used to examine this interaction. Single CHO-S cells that expressed transfected Epo receptor (Epo-R) and TRPC2 were identified, and [Ca(2+)](i) was quantitated. Epo-induced Ca(2+) influx through TRPC2 was inhibited by pretreatment with U-73122 or by downregulation of PLCgamma1 by RNA interference. PLC activation results in the production of inositol 1,4,5-trisphosphate (IP(3)), and TRPC2 has IP(3) receptor (IP(3)R) binding sites. To determine whether IP(3)R is involved in Epo-R signaling, TRPC2 mutants were prepared with partial or complete deletions of the COOH-terminal IP(3)R binding domains. In cells expressing TRPC2 IP(3)R binding mutants and Epo-R, no significant increase in [Ca(2+)](i) was observed after Epo stimulation. TRPC2 coassociated with Epo-R, PLCgamma, and IP(3)R, and the association between TRPC2 and IP(3)R was disrupted in these mutants. Our data demonstrate that Epo-R modulates TRPC2 activation through PLCgamma; that interaction of IP(3)R with TRPC2 is required; and that Epo-R, TRPC2, PLCgamma, and IP(3)R interact to form a signaling complex.
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PMID:Erythropoietin-modulated calcium influx through TRPC2 is mediated by phospholipase Cgamma and IP3R. 1532 38

TRPC3 (canonical transient receptor potential protein 3) has been suggested to be a component of cation channel complexes that are targeted to cholesterol-rich lipid membrane microdomains. In the present study, we investigated the potential role of membrane cholesterol as a regulator of cellular TRPC3 conductances. Functional experiments demonstrated that cholesterol loading activates a non-selective cation conductance and a Ca2+ entry pathway in TRPC3-overexpressing cells but not in wild-type HEK-293 (human embryonic kidney 293) cells. The cholesterol-induced membrane conductance exhibited a current-to-voltage relationship similar to that observed upon PLC (phospholipase C)-dependent activation of TRPC3 channels. Nonetheless, the cholesterol-activated conductance lacked negative modulation by extracellular Ca2+, a typical feature of agonist-activated TRPC3 currents. Involvement of TRPC3 in the cholesterol-dependent membrane conductance was further corroborated by a novel dominant-negative strategy for selective blockade of TRPC3 channel activity. Expression of a TRPC3 mutant, which contained a haemagglutinin epitope tag in the second extracellular loop, conferred antibody sensitivity to both the classical PLC-activated as well as the cholesterol-activated conductance in TRPC3-expressing cells. Moreover, cholesterol loading as well as PLC stimulation was found to increase surface expression of TRPC3. Promotion of TRPC3 membrane expression by cholesterol was persistent over 30 min, while PLC-mediated enhancement of plasma membrane expression of TRPC3 was transient in nature. We suggest the cholesterol content of the plasma membrane as a determinant of cellular TRPC3 activity and provide evidence for cholesterol dependence of TRPC3 surface expression.
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PMID:Cellular cholesterol controls TRPC3 function: evidence from a novel dominant-negative knockdown strategy. 1644 84