Partially Defective Store Operated Calcium Entry and Hem(ITAM) Signaling in Platelets of Serotonin Transporter Deficient Mice

PloS One
Karen WolfBernhard Nieswandt

Abstract

Serotonin (5-hydroxytryptamin, 5-HT) is an indolamine platelet agonist, biochemically derived from tryptophan. 5-HT is secreted from the enterochromaffin cells into the gastrointestinal tract and blood. Blood 5-HT has been proposed to regulate hemostasis by acting as a vasoconstrictor and by triggering platelet signaling through 5-HT receptor 2A (5HTR2A). Although platelets do not synthetize 5-HT, they take 5-HT up from the blood and store it in their dense granules which are secreted upon platelet activation. To identify the molecular composite of the 5-HT uptake system in platelets and elucidate the role of platelet released 5-HT in thrombosis and ischemic stroke. 5-HT transporter knockout mice (5Htt-/-) were analyzed in different in vitro and in vivo assays and in a model of ischemic stroke. In 5Htt-/- platelets, 5-HT uptake from the blood was completely abolished and agonist-induced Ca2+ influx through store operated Ca2+ entry (SOCE), integrin activation, degranulation and aggregation responses to glycoprotein VI (GPVI) and C-type lectin-like receptor 2 (CLEC-2) were reduced. These observed in vitro defects in 5Htt-/- platelets could be normalized by the addition of exogenous 5-HT. Moreover, reduced 5-HT levels in the plas...Continue Reading

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Citations

Apr 8, 2017·Nutrients·Xiao MengHua-Bin Li
Mar 28, 2017·ACS Chemical Neuroscience·Matthew J RobsonRandy D Blakely
Jun 5, 2018·Platelets·Elmina Mammadova-BachDaniel Duerschmied
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Nov 2, 2018·International Journal of Molecular Sciences·Sudip PaudelMargaret Saha
Nov 19, 2019·Frontiers in Immunology·David StegnerBernhard Nieswandt
Nov 18, 2018·Journal of Clinical Medicine·Florian PrüllerDirk von Lewinski
Mar 6, 2021·Chronobiology International·David J Kennaway
Nov 7, 2020·Journal of Thrombosis and Thrombolysis·Marina RiederDaniel Duerschmied

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Methods Mentioned

BETA
ELISA
flow cytometry
Assay
FACS

Software Mentioned

ImageJ
GPVI

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