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Characterisation of the expression profile and endothelial function of Rho GTPase RhoJ

Kaur, Sukhbir (2011)
Ph.D. thesis, University of Birmingham.

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Rho GTPases are molecular switches that regulate many aspects of cell physiology. A number of Rho GTPases are essential for the formation of new vessels from pre-existing ones, a process known as angiogenesis. RhoJ/TCL belongs to the Cdc42 subfamily of Rho GTPases. Previous bioinformatic and primary cell line analyses identified RhoJ as being highly expressed in endothelial cells. The aim of this project was to investigate the expression pattern and endothelial function of RhoJ, particularly in the processes necessary for angiogenesis. Silencing RhoJ with siRNA impaired tube formation and migration. On the cellular level, RhoJ knockdown increased focal adhesions, actin stress fibres and collagen gel contraction, suggesting increased actomyosin contractility. Pharmacological inhibition of ROCK and myosin II, two regulators of actomyosin contractility, restored motility and tube formation after RhoJ knockdown. RhoJ localised to blood vessels of developing mice and in various human normal and pathological tissues. In zebrafish embryos RhoJ was not expressed in endothelial cells, instead RhoJ was expressed in the musculature where it was involved in regulating somite formation. This study is the first to describe a role for RhoJ as a negative regulator of focal adhesion numbers and actomyosin contractility and to demonstrate a critical role of this Rho GTPase in endothelial cell migration and tube formation, thus identifying a potential new player in angiogenesis.

Type of Work:Ph.D. thesis.
Supervisor(s):Heath, Victoria L
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of immunity and infection
Subjects:R Medicine (General)
RC Internal medicine
RA Public aspects of medicine
Institution:University of Birmingham
ID Code:1558
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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