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

Kaur, Sukhbir (2011). Characterisation of the expression profile and endothelial function of Rho GTPase RhoJ. University of Birmingham. Ph.D.

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Abstract

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:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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