The membrane-associated fraction of cyclase associate protein 1 translocates to the cytosol upon platelet stimulation

Joshi, Pooja; Riley, David R.; Khalil, Jawad S.; Xiong, Huajiang; Ji, Wei; Rivero, Francisco

doi:10.1038/s41598-018-29151-w

Cited by 6 publications

(9 citation statements)

References 45 publications

(62 reference statements)

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“…3 a). Integrin αIIb and GAPDH were used as a marker of the membrane and cytosolic fractions of platelet lysates, respectively [ 36 , 37 ]. Ser24-phosphorylated Dab2 was increased in thrombin- and PAR1 peptide-stimulated platelets and was mainly found in the membrane fraction, while Ser723-phosphorylated Dab2 was mainly found in the cytosolic fraction (Fig.…”

Section: Resultsmentioning

confidence: 99%

Integrin αIIbβ3 outside-in signaling activates human platelets through serine 24 phosphorylation of Disabled-2

et al. 2021

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Background Bidirectional integrin αIIbβ3 signaling is essential for platelet activation. The platelet adaptor protein Disabled-2 (Dab2) is a key regulator of integrin signaling and is phosphorylated at serine 24 in eukaryotic cells. However, the mechanistic insight and function of Dab2-serine 24 phosphorylation (Dab2-pSer24) in platelet biology are barely understood. This study aimed to define whether and how Dab2 is phosphorylated at Ser24 during platelet activation and to investigate the effect of Dab2-pSer24 on platelet function. Results An antibody with confirmed specificity for Dab2-pSer24 was generated. By using this antibody as a tool, we showed that protein kinase C (PKC)-mediated Dab2-pSer24 was a conservative signaling event when human platelets were activated by the platelet agonists such as thrombin, collagen, ADP, 12-O-tetradecanoylphorbol-13-acetate, and the thromboxane A2 activator U46619. The agonists-stimulated Dab2-pSer24 was attenuated by pretreatment of platelets with the RGDS peptide which inhibits integrin outside-in signaling by competitive binding of integrin αIIb with fibrinogen. Direct activation of platelet integrin outside-in signaling by combined treatment of platelets with manganese dichloride and fibrinogen or by spreading of platelets on fibrinogen also resulted in Dab2-pSer24. These findings implicate that Dab2-pSer24 was associated with the outside-in signaling of integrin. Further analysis revealed that Dab2-pSer24 was downstream of Src-PKC-axis and phospholipase D1 underlying the integrin αIIbβ3 outside-in signaling. A membrane penetrating peptide R11-Ser24 which contained 11 repeats of arginine linked to the Dab2-Ser24 phosphorylation site and its flanking sequences (RRRRRRRRRRR19APKAPSKKEKK29) and the R11-S24A peptide with Ser24Ala mutation were designed to elucidate the functions of Dab2-pSer24. R11-Ser24 but not R11-S24A inhibited agonists-stimulated Dab2-pSer24 and consequently suppressed platelet spreading on fibrinogen, with no effect on platelet aggregation and fibrinogen binding. Notably, Ser24 and the previously reported Ser723 phosphorylation (Dab2-pSer723) occurred exclusively in a single Dab2 molecule and resulted in distinctive subcellular distribution and function of Dab2. Dab2-pSer723 was mainly distributed in the cytosol of activated platelets and associated with integrin inside-out signaling, while Dab2-pSer24 was mainly distributed in the membrane fraction of activated platelets and associated with integrin outside-in signaling. Conclusions These findings demonstrate for the first time that Dab2-pSer24 is conservative in integrin αIIbβ3 outside-in signaling during platelet activation and plays a novel role in the control of cytoskeleton reorganization and platelet spreading on fibrinogen.

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Section: Resultsmentioning

confidence: 99%

Integrin αIIbβ3 outside-in signaling activates human platelets through serine 24 phosphorylation of Disabled-2

et al. 2021

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“…Saponins work by stimulating the formation of new cells, or called Growth Factor. Causing the multiplication and growth of blood vessel endothelial cells, vascular smooth muscle cells and fibroblasts, causing cellular growth which ultimately repair damaged blood vessel walls [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34].…”

Section: Resultsmentioning

confidence: 99%

Bioactivity of Torch Ginger Umbut Extract (Etlingera elatior) Against Heal Wounds of Mice (Mus musculus)

Efendi

Sumarmin

Fadil

2020

Eksakta

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Torch ginger has a wide range of good antimicrobial, antioxidant, anticancer, larvicidal and repellent activities. Active compounds in Torch ginger that affect pharmacological activities are phenols, polyphenols, flavonoids, and terpenoids. Based on these ingredients Torch ginger can be used to heal wounds. This study aims to observe the effect of Torch ginger Umbut extract on wound healing in mice. This study hopes to add information about the effect of Torch ginger umbut extract on the healing of cuts in mice so that it can be another alternative for wound healing and can be a reference for other researchers. This study used a completely randomized design with 5 treatments and 3 replications. Tests carried out on adult male mice. The results showed that the optimal wound healing in P2 is treatment with 10% Torch ginger umbut extract which requires a range of wound healing 7-8 days. Based on these results, Torch ginger umbut extract can heal wounds.

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“…They are usually visible during early adhesion and spreading [ 51 ]. We have recently shown that CAP1, a protein involved in recycling of actin monomers, is also a component of the actin nodule ring [ 4 ], therefore we speculate that coronins too might contribute to the actin filament turnover of these highly dynamic structures.…”

Section: Discussionmentioning

confidence: 99%

“…Remodeling of the cytoskeleton, formed by a network of actin filaments and a marginal ring of microtubules and associated proteins constitutes a crucial aspect of platelet function and is the result of multiple exquisitely integrated signaling cascades [2]. A plethora of proteins with various biochemical activities is responsible for the dynamics of actin remodeling during platelet activation, including actin nucleators like formins and the Arp2/3 complex and their regulators (WAVE, WASP), monomeric actin-binding proteins like profilin, β-thymosin and the cyclase-associated protein (CAP) and others like gelsolin, cofilin, and coronins [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Biochemical and immunocytochemical characterization of coronins in platelets

et al. 2019

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Rapid reorganization of the actin cytoskeleton in response to receptor-mediated signaling cascades allows platelets to transition from a discoid shape to a flat spread shape upon adhesion to damaged vessel walls. Coronins are conserved regulators of the actin cytoskeleton turnover but they also participate in signaling events. To gain a better picture of their functions in platelets we have undertaken a biochemical and immunocytochemical investigation with a focus on Coro1. We found that class I coronins Coro1, 2 and 3 are abundant in human and mouse platelets whereas little Coro7 can be detected. Coro1 is mainly cytosolic, but a significant amount associates with membranes in an actin-independent manner and does not translocate from or to the membrane fraction upon exposure to thrombin, collagen or prostacyclin. Coro1 rapidly translocates to the Triton insoluble cytoskeleton upon platelet stimulation with thrombin or collagen. Coro1, 2 and 3 show a diffuse cytoplasmic localization with discontinuous accumulation at the cell cortex and actin nodules of human platelets, where all three coronins colocalize. Our data are consistent with a role of coronins as integrators of extracellular signals with actin remodeling and suggests a high extent of functional overlap among class I coronins in platelets.

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The membrane-associated fraction of cyclase associate protein 1 translocates to the cytosol upon platelet stimulation

Cited by 6 publications

References 45 publications

Integrin αIIbβ3 outside-in signaling activates human platelets through serine 24 phosphorylation of Disabled-2

Integrin αIIbβ3 outside-in signaling activates human platelets through serine 24 phosphorylation of Disabled-2

Bioactivity of Torch Ginger Umbut Extract (Etlingera elatior) Against Heal Wounds of Mice (Mus musculus)

Biochemical and immunocytochemical characterization of coronins in platelets

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