Full activation of mouse platelets requires ADP secretion regulated by SERCA3 ATPase–dependent calcium stores

Elaib, Ziane; Adam, Frédéric; Berrou, Eliane; Bordet, Jean‐Claude; Prévost, Nicolas; Bobe, Régis; Bryckaert, Marijke; Rosa, Jean‐Philippe

doi:10.1182/blood-2015-10-678383

Cited by 28 publications

(36 citation statements)

References 39 publications

(51 reference statements)

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“…32 We have recently reported that Ca 2+ mobilization from Ca 2+ stores dependent on SERCA3 but not on SERCA2b is involved in a secretion pathway important for weak agonist platelet stimulation. 33 Here, we show that this secretion of both ADP and ATP is an early secretory pathway within seconds following activation, and controlled by NAADP mobilizing Ca 2+ from SERCA3-dependent stores (heretofore designated as SERCA3 stores) and independently from inositol-3-phosphate (IP3), which in turn triggers the bulk of secretion following Ca 2+ mobilization from SERCA2b-dependent Ca 2+ stores (heretofore designated as SERCA2b stores).…”

Section: Introductionmentioning

confidence: 85%

“…We recently showed that a secretion, specifically triggered by Ca 2+ mobilization from SERCA3 stores, amplifies low agonist platelet stimulation by thrombin (through the PAR4 receptor in mouse platelets), or collagen. 33 This pathway most likely involved ADP secretion, since ADP (but not ATP) addition to thrombin rescued the defect in platelets from SERCA3 deficient (Serca3 -/-) mice, while its suppression by apyrase scavenging reduced activation of WT platelets to the level observed in Serca3 -/platelets, unaffected by apyrase. 33 However, direct evidence for SERCA3-dependent ADP release was missing, since only ATP secretion was measured.…”

Section: Serca3-dependent Adp Secretion Occurs Early and Precedes Sermentioning

confidence: 96%

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NAADP/SERCA3-Dependent Ca ²⁺ Stores Pathway Specifically Controls Early Autocrine ADP Secretion Potentiating Platelet Activation

Miao

Elaib

Borgel

et al. 2020

Circulation Research

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Rationale: Ca 2+ signaling is a key and ubiquitous actor of cell organization and its modulation controls many cellular responses. Sarco-endoplasmic reticulum Ca 2+ -ATPases (SERCAs) pump Ca 2+ into internal stores that play a major role in the cytosolic Ca 2+ concentration rise upon cell activation. Platelets exhibit 2 types of SERCAs, SERCA2b and SERCA3, which may exert specific roles, yet ill-defined. We have recently shown that Ca 2+ mobilization from SERCA3-dependent stores was required for full platelet activation in weak stimulation conditions. Objective: To uncover the signaling mechanisms associated with Ca 2+ mobilization from SERCA3-dependent stores leading to ADP secretion. Methods and Results: Using platelets from wild-type or SERCA3-deficient mice, we demonstrated that an early (within 5 to 10 seconds following stimulation) secretion of ADP specifically dependent on SERCA3 stored Ca 2+ is exclusively mobilized by nicotinic acid adenosine dinucleotide phosphate (NAADP): both Ca 2+ mobilization from SERCA3-dependent stores and primary ADP secretion are blocked by the NAADP receptor antagonist Ned-19, and reciprocally both are stimulated by permeant NAADP. In contrast, Ca 2+ mobilization from SERCA3-dependent stores and primary ADP secretion were unaffected by inhibition of the production of inositol-1,4,5-trisphosphate (IP3) by phospholipase-C, and accordingly were not stimulated by permeant IP3. Conclusions: Upon activation a NAADP/SERCA3 Ca 2+ mobilization pathway initiates an early ADP secretion, potentiating platelet activation, and a secondary wave of ADP secretion driven by both an IP3/SERCA2b-dependent Ca 2+ stores pathway and the NAADP/SERCA3 pathway. This does not exclude that Ca 2+ mobilized from SERCA3 stores may also enhance platelet global reactivity to agonists. Because of its modulating effect on platelet activation, this NAADP-SERCA3 pathway may be a relevant target for anti-thrombotic therapy.

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Section: Introductionmentioning

confidence: 85%

Section: Serca3-dependent Adp Secretion Occurs Early and Precedes Sermentioning

confidence: 96%

NAADP/SERCA3-Dependent Ca ²⁺ Stores Pathway Specifically Controls Early Autocrine ADP Secretion Potentiating Platelet Activation

Miao

Elaib

Borgel

et al. 2020

Circulation Research

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“…In that regard, it was shown that even when not causing aggregation, collagen binding to GPVI can induce platelet shape change and release of soluble platelet factors such as angiopoietin‐1, serotonin, and ATP, all of which are regulators of endothelial cell barrier function or survival . How platelet secretion and aggregation can be mechanistically uncoupled remains to be determined but a first glimpse was provided recently by studies showing the existence of specific forms and pathways of platelet secretion in response to low‐dose agonists . A recent study by Deppermann et al., showed that mice lacking platelet alpha‐ and/or dense‐granule secretion showed no signs of inflammatory bleeding in IC‐induced dermatitis or LPS‐induced lung inflammation .…”

Section: Platelets and Gpvi In Inflammationmentioning

confidence: 99%

Glycoprotein VI in securing vascular integrity in inflamed vessels

Boulaftali

Mawhin

Jandrot‐Perrus

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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Essentials Platelets can stop bleeding independently of integrin‐mediated aggregation in inflamed organs.GPVI contributes to aggregation‐independent hemostasis in the inflamed skin.GPVI supports sealing of neutrophil‐induced vascular breaches by nonaggregated platelets.Evaluation of anti‐GPVI drugs should take into account the risk of inflammatory bleeding. Glycoprotein VI (GPVI), the main platelet receptor for collagen, has been shown to play a central role in various models of thrombosis, and to be a minor actor of hemostasis at sites of trauma. These observations have made of GPVI a novel target for antithrombotic therapy, as its inhibition would ideally combine efficacy with safety. Nevertheless, recent studies have indicated that GPVI could play an important role in preventing bleeding caused by neutrophils in the inflamed skin and lungs. Remarkably, there is evidence that the GPVI‐dependent hemostatic function of platelets at the acute phase of inflammation in these organs does not involve aggregation. From a therapeutic perspective, the vasculoprotective action of GPVI in inflammation suggests that blocking of GPVI might bear some risks of bleeding at sites of neutrophil infiltration. In this review, we summarize recent findings on GPVI functions in inflammation and discuss their possible clinical implications and applications.

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“…Interestingly, comparable potentiation rates have been observed in LTP measurements of acute hippocampal slices of APPΔCT15-DM mice (APP lacking the last 15 amino acids KI—APLP2 KO mice; Klevanski et al, 2015) pointing towards a shared function for FE65 and APP at the synapse. A role for FE65 proteins at the synapse is further supported by FE65 interaction with SV2, a synaptic vesicle protein, as well as sarcoplasmatic/endoplasmatic reticulum calcium ATPase (SERCA) and ryanodine receptor (RYR; Nensa et al, 2014), involved in calcium release/homeostasis in synapses under normal physiological conditions (reviewed in Mendoza-Torreblanca et al, 2013; Del Prete et al, 2014; Elaïb et al, 2016). Interestingly, dysregulation of calcium homeostasis is discussed in pathological conditions of AD (reviewed in Small, 2009), which may involve dysregulation of this aspect of FE65 protein function.…”

Section: Fe65/fe65l1 Mutant Micementioning

confidence: 99%

APP Protein Family Signaling at the Synapse: Insights from Intracellular APP-Binding Proteins

Guénette¹,

Strecker

Kins

2017

Front. Mol. Neurosci.

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Understanding the molecular mechanisms underlying amyloid precursor protein family (APP/APP-like proteins, APLP) function in the nervous system can be achieved by studying the APP/APLP interactome. In this review article, we focused on intracellular APP interacting proteins that bind the YENPTY internalization motif located in the last 15 amino acids of the C-terminal region. These proteins, which include X11/Munc-18-interacting proteins (Mints) and FE65/FE65Ls, represent APP cytosolic binding partners exhibiting different neuronal functions. A comparison of FE65 and APP family member mutant mice revealed a shared function for APP/FE65 protein family members in neurogenesis and neuronal positioning. Accumulating evidence also supports a role for membrane-associated APP/APLP proteins in synapse formation and function. Therefore, it is tempting to speculate that APP/APLP C-terminal interacting proteins transmit APP/APLP-dependent signals at the synapse. Herein, we compare our current knowledge of the synaptic phenotypes of APP/APLP mutant mice with those of mice lacking different APP/APLP interaction partners and discuss the possible downstream effects of APP-dependent FE65/FE65L or X11/Mint signaling on synaptic vesicle release, synaptic morphology and function. Given that the role of X11/Mint proteins at the synapse is well-established, we propose a model highlighting the role of FE65 protein family members for transduction of APP/APLP physiological function at the synapse.

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Full activation of mouse platelets requires ADP secretion regulated by SERCA3 ATPase–dependent calcium stores

Abstract: Key Points• Defect in thrombus formation, platelet aggregation, and ADP secretion induced by ablation or inhibition of SERCA3

Cited by 28 publications

References 39 publications

NAADP/SERCA3-Dependent Ca ²⁺ Stores Pathway Specifically Controls Early Autocrine ADP Secretion Potentiating Platelet Activation

NAADP/SERCA3-Dependent Ca ²⁺ Stores Pathway Specifically Controls Early Autocrine ADP Secretion Potentiating Platelet Activation

Glycoprotein VI in securing vascular integrity in inflamed vessels

APP Protein Family Signaling at the Synapse: Insights from Intracellular APP-Binding Proteins

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Full activation of mouse platelets requires ADP secretion regulated by SERCA3 ATPase–dependent calcium stores

Abstract: Key Points• Defect in thrombus formation, platelet aggregation, and ADP secretion induced by ablation or inhibition of SERCA3

Cited by 28 publications

References 39 publications

NAADP/SERCA3-Dependent Ca 2+ Stores Pathway Specifically Controls Early Autocrine ADP Secretion Potentiating Platelet Activation

NAADP/SERCA3-Dependent Ca 2+ Stores Pathway Specifically Controls Early Autocrine ADP Secretion Potentiating Platelet Activation

Glycoprotein VI in securing vascular integrity in inflamed vessels

APP Protein Family Signaling at the Synapse: Insights from Intracellular APP-Binding Proteins

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Product

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NAADP/SERCA3-Dependent Ca ²⁺ Stores Pathway Specifically Controls Early Autocrine ADP Secretion Potentiating Platelet Activation

NAADP/SERCA3-Dependent Ca ²⁺ Stores Pathway Specifically Controls Early Autocrine ADP Secretion Potentiating Platelet Activation