BIN2 orchestrates platelet calcium signaling in thrombosis and thrombo-inflammation. Volz, J., Kusch, C., Beck, S., Popp, M., Vögtle, T., Meub, M., Scheller, I., Heil, H. S., Preu, J., Schuhmann, M. K., Hemmen, K., Premsler, T., Sickmann, A., Heinze, K. G., Stegner, D., Stoll, G., Braun, A., Sauer, M., & Nieswandt, B. The Journal of Clinical Investigation, 130(11):6064–6079, The American Society for Clinical Investigation, 11, 2020. ![BIN2 orchestrates platelet calcium signaling in thrombosis and thrombo-inflammation [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Store-operated Ca2+ entry (SOCE) is the major route of Ca2+ influx in platelets. The Ca2+ sensor stromal interaction molecule 1 (STIM1) triggers SOCE by forming punctate structures with the Ca2+ channel Orai1 and the inositol trisphosphate receptor (IP3R), thereby linking the endo-/sarcoplasmic reticulum to the plasma membrane. Here, we identified the BAR domain superfamily member bridging integrator 2 (BIN2) as an interaction partner of STIM1 and IP3R in platelets. Deletion of platelet BIN2 (Bin2fl/fl,Pf4-Cre mice) resulted in reduced Ca2+ store release and Ca2+ influx in response to all tested platelet agonists. These defects were a consequence of impaired IP3R function in combination with defective STIM1-mediated SOC channel activation, while Ca2+ store content and agonist-induced IP3 production were unaltered. This severely defective Ca2+ signaling translated into impaired thrombus formation under flow and a protection of Bin2fl/fl,Pf4-Cre mice in models of arterial thrombosis and stroke. Our results establish BIN2 as a central regulator of platelet activation in thrombosis and thrombo-inflammatory disease settings.
@article{volz2020orchestrates,
abstract = {Store-operated Ca2+ entry (SOCE) is the major route of Ca2+ influx in platelets. The Ca2+ sensor stromal interaction molecule 1 (STIM1) triggers SOCE by forming punctate structures with the Ca2+ channel Orai1 and the inositol trisphosphate receptor (IP3R), thereby linking the endo-/sarcoplasmic reticulum to the plasma membrane. Here, we identified the BAR domain superfamily member bridging integrator 2 (BIN2) as an interaction partner of STIM1 and IP3R in platelets. Deletion of platelet BIN2 (Bin2fl/fl,Pf4-Cre mice) resulted in reduced Ca2+ store release and Ca2+ influx in response to all tested platelet agonists. These defects were a consequence of impaired IP3R function in combination with defective STIM1-mediated SOC channel activation, while Ca2+ store content and agonist-induced IP3 production were unaltered. This severely defective Ca2+ signaling translated into impaired thrombus formation under flow and a protection of Bin2fl/fl,Pf4-Cre mice in models of arterial thrombosis and stroke. Our results establish BIN2 as a central regulator of platelet activation in thrombosis and thrombo-inflammatory disease settings.},
added-at = {2021-04-12T09:45:37.000+0200},
author = {Volz, Julia and Kusch, Charly and Beck, Sarah and Popp, Michael and Vögtle, Timo and Meub, Mara and Scheller, Inga and Heil, Hannah S. and Preu, Julia and Schuhmann, Michael K. and Hemmen, Katherina and Premsler, Thomas and Sickmann, Albert and Heinze, Katrin G. and Stegner, David and Stoll, Guido and Braun, Attila and Sauer, Markus and Nieswandt, Bernhard},
biburl = {https://www.bibsonomy.org/bibtex/24a5cecec0554523a66971339d9e282da/reichert},
doi = {10.1172/JCI136457},
interhash = {553b9fbf947cc602960ec0336f3c46a8},
intrahash = {4a5cecec0554523a66971339d9e282da},
issn = {00219738},
journal = {The Journal of Clinical Investigation},
keywords = {sauer},
month = {11},
number = 11,
pages = {6064--6079},
publisher = {The American Society for Clinical Investigation},
timestamp = {2021-04-12T09:45:37.000+0200},
title = {BIN2 orchestrates platelet calcium signaling in thrombosis and thrombo-inflammation},
url = {https://doi.org/10.1172/JCI136457},
volume = 130,
year = 2020
}
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Deletion of platelet BIN2 (Bin2fl/fl,Pf4-Cre mice) resulted in reduced Ca2+ store release and Ca2+ influx in response to all tested platelet agonists. These defects were a consequence of impaired IP3R function in combination with defective STIM1-mediated SOC channel activation, while Ca2+ store content and agonist-induced IP3 production were unaltered. This severely defective Ca2+ signaling translated into impaired thrombus formation under flow and a protection of Bin2fl/fl,Pf4-Cre mice in models of arterial thrombosis and stroke. 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