Novel Role of Ras-GTPase Activating Protein SH3 Domain-Binding Protein G3BP in Adhesion and Migration of 32D Myeloid Progenitor Cells



Kerstin Schwarz1, Frank Aschenbrenner1, Brigitte Ruster2, Manuela Kampfmann1, Martina Komor1, Wolf-Karsten Hofmann3, Martin Ruthardt1, Reinhard Henschler2, Gesine Bug1, *
1 Department of Medicine II, Hematology and Oncology, Johann Wolfgang Goethe University Frankfurt, Germany
2 Institute of Transfusion Medicine and Immune Hematology, German Red Cross Blood Donor Service Baden- Württemberg - Hessen, Clinics of the Goethe University, Frankfurt, Germany
3 Department of Hematology and Oncology, Medical Faculty Mannheim of the University Heidelberg-Mannheim, Germany


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© 2012 Schwarzet al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Medicine II, Hematology and Oncology, Johann Wolfgang Goethe University, Theodor- Stern-Kai 7, 60590 Frankfurt, Germany; Tel: +49-69-6301-7760; Fax: +49-69-6301-7790; E-mail: g.bug@em.uni-frankfurt.de


Abstract

Rho GTPases are involved in homing and mobilization of hematopoietic stem and progenitor cells due to their impact on cytoskeleton remodeling. We have previously shown that inhibition of Rho, Rac and Cdc42 clearly impairs adhesion of normal and leukemic hematopoietic progenitor cells (HPC) to fibronectin and migration in a three-dimensional stromal cell model. Here, we identified the Ras GTPase-Activating Protein SH3 Domain-Binding Protein (G3BP) as a target gene of Rho GTPases and analysed its role in regulating HPC motility. Overexpression of G3BP significantly enhanced adhesion of murine 32D HPC to fibronectin and human umbilical vein endothelial cells, increased the proportion of adherent cells in a flow chamber assay and promoted cell migration in a transwell assay and a three-dimensional stromal cell model suggesting a strong impact on the cytoskeleton. Immunofluorescent staining of G3BP-overexpressing fibroblasts revealed a Rho-like phenotype characterized by formation of actin stress fibers in contrast to the Rac-like phenotype of control fibroblasts. This is the first report implicating a role for G3BP in Rho GTPase-mediated signalling towards adhesion and migration of HPC. Our results may be of clinical importance, since G3BP was found overexpressed in human cancers.

Keywords: G3BP, Rho GTPases, 32D progenitor cells, adhesion, migration, homing, toxin B, lethal toxin.