Thrombin-sensitive expression of the store operated Ca(2+) channel Orai1 in platelets
Copyright © 2013 Elsevier Inc. All rights reserved..
Thrombin activates pore forming channel protein Orai1 resulting in store operated Ca(2+) entry (SOCE) with subsequent Ca(2+)-dependent release of platelet granules, activation of integrin αIIbβ3, adhesion, aggregation and thrombus formation. Platelets lack nuclei and are thus unable to modify protein abundance by transcriptional regulation. Nevertheless, they still contain pre-mRNA and mRNA and are thus able to express protein by stimulation of rapid translation. Platelet translation is sensitive to phosphoinositide-3-kinase (PI3K) and actin polymerization. The present study explored whether platelet activation via thrombin modifies Orai1 protein abundance. According to RT-PCR platelets contain pre-mRNA and mRNA encoding Orai1. Activation with thrombin (0.1 U/ml) results in a significant decline of pre-mRNA, which is, according to Western blotting and confocal microscopy, paralleled by a marked and statistically significant increase of Orai1 protein abundance. The increase of Orai1 protein abundance is insensitive to inhibition of transcription with actinomycin (4 μg/ml), but is significantly blunted by inhibition of translation with puromycin (100 nM) and by inhibition of PI3K with wortmannin (100 nM) or LY294002 (25 μM). In conclusion, activation of platelets stimulates the translational expression of Orai1, thus augmenting platelet Ca(2+) signaling.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2013 |
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| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:436 |
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| Enthalten in: |
Biochemical and biophysical research communications - 436(2013), 1 vom: 21. Juni, Seite 25-30 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Münzer, Patrick [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.08.2013 Date Revised 03.12.2018 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbrc.2013.05.031 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM227604377 |
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| 245 | 1 | 0 | |a Thrombin-sensitive expression of the store operated Ca(2+) channel Orai1 in platelets |
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| 500 | |a Date Revised 03.12.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2013 Elsevier Inc. All rights reserved. | ||
| 520 | |a Thrombin activates pore forming channel protein Orai1 resulting in store operated Ca(2+) entry (SOCE) with subsequent Ca(2+)-dependent release of platelet granules, activation of integrin αIIbβ3, adhesion, aggregation and thrombus formation. Platelets lack nuclei and are thus unable to modify protein abundance by transcriptional regulation. Nevertheless, they still contain pre-mRNA and mRNA and are thus able to express protein by stimulation of rapid translation. Platelet translation is sensitive to phosphoinositide-3-kinase (PI3K) and actin polymerization. The present study explored whether platelet activation via thrombin modifies Orai1 protein abundance. According to RT-PCR platelets contain pre-mRNA and mRNA encoding Orai1. Activation with thrombin (0.1 U/ml) results in a significant decline of pre-mRNA, which is, according to Western blotting and confocal microscopy, paralleled by a marked and statistically significant increase of Orai1 protein abundance. The increase of Orai1 protein abundance is insensitive to inhibition of transcription with actinomycin (4 μg/ml), but is significantly blunted by inhibition of translation with puromycin (100 nM) and by inhibition of PI3K with wortmannin (100 nM) or LY294002 (25 μM). In conclusion, activation of platelets stimulates the translational expression of Orai1, thus augmenting platelet Ca(2+) signaling | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Calcium Channels |2 NLM | |
| 650 | 7 | |a Chromones |2 NLM | |
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| 700 | 1 | |a Pelzl, Lisann |e verfasserin |4 aut | |
| 700 | 1 | |a Schmid, Evi |e verfasserin |4 aut | |
| 700 | 1 | |a Schmidt, Eva-Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Walker, Britta |e verfasserin |4 aut | |
| 700 | 1 | |a Fröhlich, Henning |e verfasserin |4 aut | |
| 700 | 1 | |a Borst, Oliver |e verfasserin |4 aut | |
| 700 | 1 | |a Gawaz, Meinrad |e verfasserin |4 aut | |
| 700 | 1 | |a Lang, Florian |e verfasserin |4 aut | |
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