scholarly journals Stabilization of Cortical Actin Induces Internalization of Transient Receptor Potential 3 (Trp3)-associated Caveolar Ca2+Signaling Complex and Loss of Ca2+Influx without Disruption of Trp3-Inositol Trisphosphate Receptor Association

2001 ◽  
Vol 276 (45) ◽  
pp. 42401-42408 ◽  
Author(s):  
Timothy Lockwich ◽  
Brij B. Singh ◽  
Xibao Liu ◽  
Indu S. Ambudkar
Keyword(s):  
Transient Receptor Potential ◽  
Inositol Trisphosphate ◽  
Receptor Potential ◽  
Cortical Actin ◽  
Inositol Trisphosphate Receptor ◽  
Signaling Complex ◽  
Transient Receptor ◽  
Trisphosphate Receptor

scholarly journals Transient Receptor Potential Canonical 5-Scramblase Signaling Complex Mediates Neuronal Phosphatidylserine Externalization and Apoptosis

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 547 ◽  
Author(s):  
Jizheng Guo ◽  
Jie Li ◽  
Lin Xia ◽  
Yang Wang ◽  
Jinhang Zhu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Cortical Neurons ◽  
Transient Receptor Potential ◽  
Ischemia Reperfusion ◽  
Receptor Potential ◽  
Hek293 Cells ◽  
Wild Type ◽  
Signaling Complex ◽  
Cerebral Ischemia Reperfusion ◽  
Transient Receptor

Phospholipid scramblase 1 (PLSCR1), a lipid-binding and Ca2+-sensitive protein located on plasma membranes, is critically involved in phosphatidylserine (PS) externalization, an important process in cell apoptosis. Transient receptor potential canonical 5 (TRPC5), is a nonselective Ca2+ channel in neurons that interacts with many downstream molecules, participating in diverse physiological functions including temperature or mechanical sensation. The interaction between TRPC5 and PLSCR1 has never been reported. Here, we showed that PLSCR1 interacts with TRPC5 through their C-termini in HEK293 cells and mouse cortical neurons. Formation of TRPC5-PLSCR1 complex stimulates PS externalization and promotes cell apoptosis in HEK293 cells and mouse cerebral neurons. Furthermore, in vivo studies showed that PS externalization in cortical neurons induced by artificial cerebral ischemia-reperfusion was reduced in TRPC5 knockout mice compared to wild-type mice, and that the percentage of apoptotic neurons was also lower in TRPC5 knockout mice than in wild-type mice. Collectively, the present study suggested that TRPC5-PLSCR1 is a signaling complex mediating PS externalization and apoptosis in neurons and that TRPC5 plays a pathological role in cerebral-ischemia reperfusion injury.

scholarly journals Pregnancy-enhanced store-operated Ca2+ channel function in uterine artery endothelial cells is associated with enhanced agonist-specific transient receptor potential channel 3-inositol 1,4,5-trisphosphate receptor 2 interaction

2006 ◽  
Vol 190 (2) ◽  
pp. 385-395 ◽  
Author(s):  
Shannon M Gifford ◽  
Fu-Xian Yi ◽  
Ian M Bird
Keyword(s):  
Endothelial Cells ◽  
Uterine Artery ◽  
Transient Receptor Potential ◽  
Purinergic Receptor ◽  
Receptor Potential ◽  
Cell Types ◽  
Transient Receptor Potential Channels ◽  
Significant Difference ◽  
Transient Receptor ◽  
Trisphosphate Receptor

We have previously shown that endothelial cells (EC) derived from the uterine artery (UA) of both pregnant (P-UAEC) and nonpregnant (NP-UAEC) ewes show a biphasic intracellular free Ca2+ ([Ca2+]i) response after ATP stimulation. In each case, the initial transient peak, caused by the release of Ca2+ from the intracellular Ca2+ stores, is mediated by purinergic receptor-Y2 and is very similar in both cell types. However, the sustained phase in particular, caused by the influx of extracellular Ca2+, is heightened in the P-UAEC, and associates with an increased ability of the cells to demonstrate enhanced capacitative Ca2+ entry (CCE) via store-operated channels (SOCs). Herein we demonstrated that the difference in the sustained [Ca2+]i response is maintained for at least 30 min. When 2-aminoethoxydiphenyl borate (2APB) (an inhibitor of the inosital 1,4,5-trisphosphate receptor (IP3R) and possibly SOC) was used in conjunction with ATP, it was capable of completely inhibiting CCE. Since 2APB can inhibit SOC in some cell types and 2APB was capable of inhibiting CCE in the UAEC model, the role of SOC in CCE was first evaluated using the classical inhibitor La3+. The ATP-induced sustained phase was inhibited by 10 μM La3+, implying a role for SOC in the [Ca2+]i response. Since canonical transient receptor potential channels (TRPCs) have recently been identified as putative SOCs in many cell types, including EC, the expression levels of several isoforms were evaluated in UAEC. Expression of TRPC3 and TRPC6 channels in particular was detected, but no significant difference in expression level was found between NP- and P-UAEC. Nonetheless, we were able to show that IP3R2 interacts with TRPC3 in UAEC, forming a protein complex, and that this interaction is considerably enhanced in an agonist sensitive manner by pregnancy. Thus, while IP3R and TRPC isoforms are not altered in their expression by pregnancy, enhanced functional interaction of TRPC3 with IP3R2 may underlie pregnancy-enhanced CCE in the UAEC model and so explain the prolonged [Ca2+]i sustained phase seen in response to ATP.

Erythropoietin-modulated calcium influx through TRPC2 is mediated by phospholipase Cγ and IP3R

2004 ◽  
Vol 287 (6) ◽  
pp. C1667-C1678 ◽  
Author(s):  
Qin Tong ◽  
Xin Chu ◽  
Joseph Y. Cheung ◽  
Kathleen Conrad ◽  
Richard Stahl ◽  
...  
Keyword(s):  
Calcium Concentration ◽  
Transient Receptor Potential ◽  
Calcium Influx ◽  
Receptor Potential ◽  
Signaling Complex ◽  
Binding Domains ◽  
Transient Receptor ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Inactive Analog

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 ([Ca2+]i). This increase in [Ca2+]iwas 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 Ca2+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 [Ca2+]iwas quantitated. Epo-induced Ca2+influx through TRPC2 was inhibited by pretreatment with U-73122 or by downregulation of PLCγ1 by RNA interference. PLC activation results in the production of inositol 1,4,5-trisphosphate (IP3), and TRPC2 has IP3receptor (IP3R) binding sites. To determine whether IP3R is involved in Epo-R signaling, TRPC2 mutants were prepared with partial or complete deletions of the COOH-terminal IP3R binding domains. In cells expressing TRPC2 IP3R binding mutants and Epo-R, no significant increase in [Ca2+]iwas observed after Epo stimulation. TRPC2 coassociated with Epo-R, PLCγ, and IP3R, and the association between TRPC2 and IP3R was disrupted in these mutants. Our data demonstrate that Epo-R modulates TRPC2 activation through PLCγ; that interaction of IP3R with TRPC2 is required; and that Epo-R, TRPC2, PLCγ, and IP3R interact to form a signaling complex.

Flickering calcium microdomains signal turning of migrating cellsThis article is one of a selection of papers published in this special issue on Calcium Signaling.

2010 ◽  
Vol 88 (2) ◽  
pp. 105-110 ◽  
Author(s):  
Chaoliang Wei ◽  
Xianhua Wang ◽  
Min Chen ◽  
Kunfu Ouyang ◽  
Ming Zheng ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
High Threshold ◽  
Calcium Dependent ◽  
A Cell ◽  
Transient Receptor ◽  
Trisphosphate Receptor ◽  
Selection Of

It has been well-established that polarized migrating cells exhibit a stable and transient gradient of intracellular calcium concentration ([Ca2+]i), increasing from front-to-rear, that is thought to be responsible for rear retraction. The paradox that arises is how calcium at the front of a cell catalyzes critical high-threshold calcium-dependent processes during cell migration and particularly in decision-making for a cell to turn. In this brief review, we discuss the recent discovery of flickering high-[Ca2+]i microdomains (“calcium flickers”) at the front of migrating fibroblasts and their common role in transducing local membrane mechanical stress (via TRPM7, a stretch-activated calcium-permeating transient receptor potential channel) and chemoattractant-elicited signals (via type 2 inositol 1,4,5-trisphosphate receptor in the endoplasmic reticulum). Furthermore, we present a new model for patterned calcium flicker activity as the mechanism for steering the turning of a migrating cell.

scholarly journals Rapid agonist-evoked coupling of type II Ins(1,4,5)P3 receptor with human transient receptor potential (hTRPC1) channels in human platelets

2003 ◽  
Vol 375 (3) ◽  
pp. 697-704 ◽  
Author(s):  
Sharon L. BROWNLOW ◽  
Stewart O. SAGE
Keyword(s):  
Transient Receptor Potential ◽  
De Novo ◽  
Receptor Potential ◽  
Coupling Model ◽  
Human Platelets ◽  
Type Ii ◽  
Bivalent Cation ◽  
Store Depletion ◽  
Transient Receptor ◽  
Trisphosphate Receptor

Depletion of intracellular Ca2+ stores results in the activation of SMCE (store-mediated Ca2+ entry) in many cells. The mechanism of activation of SMCE is poorly understood. In human platelets, a secretion-like coupling model may be involved. This proposes that store depletion results in trafficking of portions of the endoplasmic reticulum to the plasma membrane, enabling coupling between proteins in the two membranes. In support of this, we have shown that, in human platelets, agonist-evoked Ca2+ store depletion results in de novo and reversible coupling of the InsP3RII [type II inositol (1,4,5)trisphosphate receptor] with the putative Ca2+ entry channel hTRPC1 [human canonical transient receptor potential 1 (protein); Rosado, Brownlow and Sage (2002) J. Biol. Chem. 277, 42157–42163]. A crucial test of the hypothesis that this coupling activates SMCE is that it should occur rapidly enough to account for agonist-evoked Ca2+ entry. In the present study, we have used quenched- and stopped-flow approaches to determine the latencies of thrombin-evoked coupling of InsP3RII with hTRPC1 and of thrombin-evoked bivalent cation entry using Mn2+ quenching of fura 2 fluorescence. Thrombin-evoked Mn2+ entry was detected with a latency of 0.81±0.07 s (S.E.M., n=7) or 1.36±0.09 s (S.E.M., n=7) at a concentration of 1.0 or 0.1 unit/ml respectively. Coupling between InsP3RII and hTRPC1, assessed at 100 ms intervals, was first detected with a latency of 0.9 or 1.4 s after stimulation with thrombin at a concentration of 1.0 or 0.1 unit/ml respectively. These results support the hypothesis that de novo coupling of InsP3RII with hTRPC1 could activate SMCE in human platelets.

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