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- Title
Chorein sensitivity of cytoskeletal organization and degranulation of platelets.
- Authors
Schmidt, Eva-Maria; Schmid, Evi; Münzer, Patrick; Hermann, Andreas; Eyrich, Ann-Kathrin; Russo, Antonella; Walker, Britta; Shuchen Gu; Müller vom Hagen, Jennifer; Faggio, Caterina; Schaller, Martin; Föller, Michael; Schöls, Ludger; Gawaz, Meinrad; Borst, Oliver; Storch, Alexander; Stournaras, Christos; Lang, Florian
- Abstract
Chorea-acanthocytosis (ChAc), a lethal disease caused by defective chorein, is characterized by neurodegeneration and erythrocyte acanthocytosis. The functional significance of chorein in other cell types remained ill-defined. The present study revealed chorein expression in blood platelets. As compared to platelets from healthy volunteers, platelets from patients with ChAc displayed a 47% increased globular/filamentous actin ratio, indicating actin depolymerization. Moreover, phosphoinositide-3-kinase subunit p85 phosphorylation, p21 protein-activated kinase (PAK1) phosphorylation, as well as vesicle-associated membrane protein 8 (VAMP8) expression were significantly reduced in platelets from patients with ChAc (by 17, 22, and 39%, respectively) and in megakaryocytic (MEG-01) cells following chorein silencing (by 16, 54, and 11%, respectively). Activation-induced platelet secretion from dense granules (ATP release) and α granules (P-selectin exposure) were significantly less (by 55% after stimulation with 1 µg/ml CRP and by 33% after stimulation with 5 µM TRAP, respectively) in ChAc platelets than in control platelets. Furthermore, platelet aggregation following stimulation with different platelet agonists was significantly impaired. These observations reveal a completely novel function of chorein, i.e., regulation of secretion and aggregation of blood platelets.
- Subjects
CHOREA; BIOLOGICAL aggregation; BLOOD platelets; BLOOD platelet aggregation; DEPOLYMERIZATION
- Publication
FASEB Journal, 2013, Vol 27, Issue 7, p2799
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.13-229286