دورية أكاديمية
Tspan18 is a novel regulator of the Ca 2+ channel Orai1 and von Willebrand factor release in endothelial cells.
| العنوان: | Tspan18 is a novel regulator of the Ca 2+ channel Orai1 and von Willebrand factor release in endothelial cells. |
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| المؤلفون: | Noy PJ; School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, UK., Gavin RL; School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, UK., Colombo D; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK., Haining EJ; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK., Reyat JS; School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, UK., Payne H; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK., Thielmann I; University Hospital Würzburg and Rudolf Virchow Center for Experimental Biomedicine, Würzburg, Germany., Lokman AB; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK., Neag G; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK., Yang J; School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, UK., Lloyd T; School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, UK., Harrison N; School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, UK., Heath VL; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK., Gardiner C; Department of Haematology, University College London, London, UK., Whitworth KM; Institute of Immunology and Immunotherapy, Cancer Immunology and Immunotherapy Centre, University of Birmingham, Birmingham, UK., Robinson J; Institute of Immunology and Immunotherapy, Cancer Immunology and Immunotherapy Centre, University of Birmingham, Birmingham, UK., Koo CZ; School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, UK., Di Maio A; School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, UK., Harrison P; Scar Free Foundation for Burns Research, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham National Health Service (NHS) Foundation Trust, Birmingham, UK.; Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK., Lee SP; Institute of Immunology and Immunotherapy, Cancer Immunology and Immunotherapy Centre, University of Birmingham, Birmingham, UK., Michelangeli F; Department of Biological Sciences, University of Chester, Chester, UK., Kalia N; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.; Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, Birmingham-Nottingham, UK., Rainger GE; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK., Nieswandt B; University Hospital Würzburg and Rudolf Virchow Center for Experimental Biomedicine, Würzburg, Germany., Brill A; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.; Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, Birmingham-Nottingham, UK.; Department of Pathophysiology, Sechenov First Moscow State Medical University, Moscow, Russia., Watson SP; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.; Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, Birmingham-Nottingham, UK., Tomlinson MG; School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, UK m.g.tomlinson@bham.ac.uk.; Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, Birmingham-Nottingham, UK. |
| المصدر: | Haematologica [Haematologica] 2019 Sep; Vol. 104 (9), pp. 1892-1905. Date of Electronic Publication: 2018 Dec 20. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Ferrata Storti Foundation Country of Publication: Italy NLM ID: 0417435 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1592-8721 (Electronic) Linking ISSN: 03906078 NLM ISO Abbreviation: Haematologica Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1999- : Pavia, Italy : Ferrata Storti Foundation Original Publication: Pavia [etc.] |
| مواضيع طبية MeSH: | Calcium/*metabolism , Myocardial Reperfusion Injury/*genetics , ORAI1 Protein/*genetics , Tetraspanins/*genetics , Venous Thrombosis/*genetics , von Willebrand Factor/*genetics, Animals ; B-Lymphocytes/cytology ; B-Lymphocytes/drug effects ; B-Lymphocytes/metabolism ; Chickens ; Disease Models, Animal ; Gene Expression Regulation ; HEK293 Cells ; HeLa Cells ; Histamine/pharmacology ; Human Umbilical Vein Endothelial Cells/cytology ; Human Umbilical Vein Endothelial Cells/drug effects ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; Ion Transport/drug effects ; Jurkat Cells ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myocardial Reperfusion Injury/metabolism ; Myocardial Reperfusion Injury/pathology ; NFATC Transcription Factors/genetics ; NFATC Transcription Factors/metabolism ; ORAI1 Protein/metabolism ; Signal Transduction ; Tetraspanins/metabolism ; Thrombin/pharmacology ; Venous Thrombosis/metabolism ; Venous Thrombosis/pathology ; von Willebrand Factor/metabolism |
| مستخلص: | Ca 2+ entry via Orai1 store-operated Ca 2+ channels in the plasma membrane is critical to cell function, and Orai1 loss causes severe immunodeficiency and developmental defects. The tetraspanins are a superfamily of transmembrane proteins that interact with specific 'partner proteins' and regulate their trafficking and clustering. The aim of this study was to functionally characterize tetraspanin Tspan18. We show that Tspan18 is expressed by endothelial cells at several-fold higher levels than most other cell types analyzed. Tspan18-knockdown primary human umbilical vein endothelial cells have 55-70% decreased Ca 2+ mobilization upon stimulation with the inflammatory mediators thrombin or histamine, similar to Orai1-knockdown. Tspan18 interacts with Orai1, and Orai1 cell surface localization is reduced by 70% in Tspan18-knockdown endothelial cells. Tspan18 overexpression in lymphocyte model cell lines induces 20-fold activation of Ca 2+ -responsive nuclear factor of activated T cell (NFAT) signaling, in an Orai1-dependent manner. Tspan18-knockout mice are viable. They lose on average 6-fold more blood in a tail-bleed assay. This is due to Tspan18 deficiency in non-hematopoietic cells, as assessed using chimeric mice. Tspan18-knockout mice have 60% reduced thrombus size in a deep vein thrombosis model, and 50% reduced platelet deposition in the microcirculation following myocardial ischemia-reperfusion injury. Histamine- or thrombin-induced von Willebrand factor release from endothelial cells is reduced by 90% following Tspan18-knockdown, and histamine-induced increase of plasma von Willebrand factor is reduced by 45% in Tspan18-knockout mice. These findings identify Tspan18 as a novel regulator of endothelial cell Orai1/Ca 2+ signaling and von Willebrand factor release in response to inflammatory stimuli. (Copyright© 2019 Ferrata Storti Foundation.) |
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| معلومات مُعتمدة: | RG/12/7/29693 United Kingdom BHF_ British Heart Foundation; FS/08/062/25797 United Kingdom BHF_ British Heart Foundation; G0400247 United Kingdom MRC_ Medical Research Council; PG/13/92/30587 United Kingdom BHF_ British Heart Foundation; FS/18/9/33388 United Kingdom BHF_ British Heart Foundation; FS/14/42/30956 United Kingdom BHF_ British Heart Foundation; FS/12/79/29871 United Kingdom BHF_ British Heart Foundation |
| المشرفين على المادة: | 0 (NFATC Transcription Factors) 0 (ORAI1 Protein) 0 (ORAI1 protein, human) 0 (TSPAN18 protein, human) 0 (Tetraspanins) 0 (von Willebrand Factor) 820484N8I3 (Histamine) EC 3.4.21.5 (Thrombin) SY7Q814VUP (Calcium) |
| تواريخ الأحداث: | Date Created: 20181222 Date Completed: 20200615 Latest Revision: 20231013 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC6717597 |
| DOI: | 10.3324/haematol.2018.194241 |
| PMID: | 30573509 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1592-8721 |
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| DOI: | 10.3324/haematol.2018.194241 |