Chorein sensitivity of cytoskeletal organization and degranulation of platelets
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 comp...
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Published in | The FASEB journal Vol. 27; no. 7; p. 2799 |
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Main Authors | , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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United States
01.07.2013
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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. |
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AbstractList | 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. |
Author | Walker, Britta Faggio, Caterina Borst, Oliver Storch, Alexander Münzer, Patrick Föller, Michael Lang, Florian Eyrich, Ann-Kathrin Hermann, Andreas Gu, Shuchen Gawaz, Meinrad Schaller, Martin Schöls, Ludger Schmidt, Eva-Maria vom Hagen, Jennifer Müller Schmid, Evi Stournaras, Christos Russo, Antonella |
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SubjectTerms | Actins - metabolism Adult Blood Platelets - metabolism Blood Platelets - physiology Blood Platelets - ultrastructure Blotting, Western Cell Degranulation Cell Line, Tumor Class Ia Phosphatidylinositol 3-Kinase - metabolism Cytoskeleton - metabolism Female Humans Male Microscopy, Confocal Microscopy, Electron, Transmission Middle Aged Neuroacanthocytosis - blood Neuroacanthocytosis - genetics Neuroacanthocytosis - metabolism p21-Activated Kinases - metabolism Phosphorylation Platelet Aggregation R-SNARE Proteins - metabolism RNA Interference Vesicular Transport Proteins - genetics Vesicular Transport Proteins - metabolism Young Adult |
Title | Chorein sensitivity of cytoskeletal organization and degranulation of platelets |
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