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Acta Physiologica 2013; Volume 207, Supplement 694
92nd Annual Meeting of the German Physiological Society
3/2/2013-3/5/2013
Heidelberg, Germany
ACTIN DEPOLYMERIZATION AND IMPAIRED DEGRANULATION OF PLATELETS FROM PATIENTS WITH CHOREOACANTHOCYTOSIS
Abstract number: P175
Russo
*A.
, Schmidt
1
E., Schmid
1
E., Münzer
1
P., Hermann
3
A., Eyrich
1
A., Walker
1
B., Gu
1
S., vom Hagen
4
J., Faggio
2
C., Schaller
5
M., Alesutan
1
I., Föller
1
M., Schöls
3
L., Borst O., Gawaz M
6
M., Storch A
3
A., Stournaras
1
C., Lang
1
F.
1
University of Tuebingen, Department of Physiology, Tübingen, Germany
2
University of Messina, Department of Biological and Environmental Sciences, Messina, Italy
3
University of Dresden, Department of Neurology, Dresden, Germany
4
University of Tuebingen, Neurology, Tuebingen, Germany
5
University of Tuebingen, Dermatology, Tuebingen, Germany
6
University of Tuebingen, Cardiology and Cardiovascular Medicine, Tübingen, Germany
Background:
Chorea-acanthocytosis, a lethal disease caused by defective chorein, is characterized by progressive hyperkinetic movement disorder, cognitive and behavioural abnormalities as well as acanthocytosis. Recent observations revealed decreased phosphoinositide-3-kinase (PI3K) and p21 protein-activated kinase (PAK) 1 phosphorylation as well as actin depolymerization in erythrocytes from chorea-acanthocytosis patients and in K562-erythrocytic cells following chorein silencing. Chorein is expressed in a wide variety of further cells including blood platelets. The present study thus compared properties of platelets from patients with chorea-acanthocytosis with platelets from healthy volunteers.
Methods:
Abundance of polymerized and depolymerized actin, of total and phosphorylated PI3K-p85-subunit, of total and phosphorylated PAK1, as well as of the degranulation regulating vesicle-associated membrane protein 8 (VAMP8) were determined by western blotting, activation induced P-selectin exposure was determined by FACS analysis, and ATP release utilizing the luciferin-luciferase assay.
Results:
Actin was less polymerized in platelets from patients with chorea-acanthocytosis (ChAc) than in platelets from healthy volunteers (control). Moreover, PI3K-p85-subunit phosphorylation, PAK1 phosphorylation, VAMP8 protein abundance, activation induced P-selectin exposure and ATP release, and platelet aggregation were less pronounced in ChAc platelets than in control platelets. Chorein silencing of MEG01 cells resulted in decreased PAK1 phosphorylation and VAMP8 expression.
Conclusions:
The observations reveal a completely novel function of chorein, i.e. regulation of cytoskeleton, PI3K signaling and degranulation of blood platelets.
To cite this abstract, please use the following information:
Acta Physiologica 2013; Volume 207, Supplement 694 :P175