RhoGAPs und Rho-GTPasen in Thrombozyten

Margitta Elvers

doi:10.5482/HAMO-14-09-0046

Hämostaseologie, Table of Contents

Hamostaseologie 2016; 36(03): 168-177
DOI: 10.5482/HAMO-14-09-0046

Review

Schattauer GmbH

RhoGAPs und Rho-GTPasen in Thrombozyten

RhoGAPs and Rho GTPases in platelets

Authors

Margitta Elvers

¹Department of Clinical and Experimental Hemostasis, Hemotherapy and Transfusion Medicine, Heinrich-Heine-University, Düsseldorf, Germany

Abstract

Zusammenfassung

Die Reorganisation des Zytoskeletts in Thrombozyten ist essenziell für die Thrombozytenadhäsion und Thrombusbildung in Hämostase und Thrombose. Die Rho-GTPasen RhoA, Rac1 und Cdc42 spielen eine entscheidende Rolle bei der Reorganisation des Zytoskeletts, indem sie die Bildung von Filopodien und Lamellipodien induzieren und somit für die Oberflächenvergrößerung der Thrombozyten wäh-rend der Aktivierung verantwortlich sind. Rho-GTPasen beeinflussen zudem die Prozesse der Thrombozytenaktivität und Aggregatbildung durch Modulation der Sekretion, Integrinaktivierung und arteriellen Thrombusbildung. Die Aktivität der Rho-GTPasen wird von verschiedenen Proteinen kontrolliert, z. B. den GTPase aktivierenden Proteinen (GTPase activating proteins, GAPs). GAPs lösen die Inaktivierung des Guaninnukleotidbindenden Proteins durch Stimulierung der GTPase-Aktivität aus. Die Rolle und Bedeutung von GAPs in Thrombozyten ist nur wenig verstanden und viele der bekannten Rho-GAPs sind bisher nicht in Thrombozyten identifiziert oder hinsichtlich ihrer Funktion charakterisiert worden. Die kürzlich entdeckten RhoGAPs Oligophrenin1 (OPHN1) und Nadrin regulieren die Aktivität von RhoA, Rac1 und Cdc42 und nachfolgend die Reorganisation des Zytoskeletts und die Aktivierung von Thrombozyten sowie die Thrombusbildung. In den letzten Jahren trug die Analyse gene-tisch-modifizierter Mäuse dazu bei, grundlegende Erkenntnisse zur Bedeutung von RhoGTPasen und ihren Regulatoren für die Reorganisation des Zytoskeletts und andere Rhovermittelte zelluläre Prozesse in Thrombozyten zu gewinnen.

Summary

Platelet cytoskeletal reorganization is essential for platelet adhesion and thrombus formation in hemostasis and thrombosis. The Rho GTPases RhoA, Rac1 and Cdc42 are the main players in cytoskeletal dynamics of platelets responsible for the formation of filopodia and lamellipodia to strongly increase the platelet surface upon activation. They are involved in platelet activation and aggregate formation including platelet secretion, inte-grin activation and arterial thrombus formation. The activity of Rho GTPases is tightly controlled by different proteins such as GTPase-activating proteins (GAPs). GAPs stimulate GTP hydrolysis to terminate Rho signaling. The role and impact of GAPs in platelets is not well-defined and many of the RhoGAPs identified are not known to be present in platelets or to have any function in platelets. The recently identified RhoGAPs Oligophrenin1 (OPHN1) and Nadrin regulate the activity of RhoA, Rac1 and Cdc42 and subsequent platelet cytoskeletal reorganization, platelet activation and thrombus formation. In the last years, the analysis of genetically modified mice helped to gain the understanding of Rho GTPases and their regulators in cytoskeletal rearrangements and other Rho mediated cellular processes in platelets.

Schlüsselwörter

Zytoskelett - Thrombozyten - Rho-GTPasen - Rho-GAP - Oligophrenin 1

Keywords

Cytoskeleton - platelet - Rho GTPases - RhoGAP - nadrin - oligophrenin1

Full Text

References

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