The WASH-complex subunit Strumpellin regulates integrin αIIbβ3 trafficking in murine platelets

The platelet specific integrin αIIbβ3 mediates platelet adhesion, aggregation and plays a central role in thrombosis and hemostasis. In resting platelets, αIIbβ3 is expressed on the membrane surface and in intracellular compartments. Upon activation, the number of surface-expressed αIIbβ3 is increas...

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Veröffentlicht in:Scientific reports 2023-06, Vol.13 (1), p.9526-9526, Article 9526
Hauptverfasser: Schurr, Yvonne, Reil, Lucy, Spindler, Markus, Nieswandt, Bernhard, Machesky, Laura M., Bender, Markus
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Sprache:eng
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Zusammenfassung:The platelet specific integrin αIIbβ3 mediates platelet adhesion, aggregation and plays a central role in thrombosis and hemostasis. In resting platelets, αIIbβ3 is expressed on the membrane surface and in intracellular compartments. Upon activation, the number of surface-expressed αIIbβ3 is increased by the translocation of internal granule pools to the plasma membrane. The WASH complex is the major endosomal actin polymerization-promoting complex and has been implicated in the generation of actin networks involved in endocytic trafficking of integrins in other cell types. The role of the WASH complex and its subunit Strumpellin in platelet function is still unknown. Here, we report that Strumpellin-deficient murine platelets display an approximately 20% reduction in integrin αIIbβ3 surface expression. While exposure of the internal αIIbβ3 pool after platelet activation was unaffected, the uptake of the αIIbβ3 ligand fibrinogen was delayed. The number of platelet α-granules was slightly but significantly increased in Strumpellin-deficient platelets. Quantitative proteome analysis of isolated αIIbβ3-positive vesicular structures revealed an enrichment of protein markers, which are associated with the endoplasmic reticulum, Golgi complex and early endosomes in Strumpellin-deficient platelets. These results point to a so far unidentified role of the WASH complex subunit Strumpellin in integrin αIIbβ3 trafficking in murine platelets.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-36387-8