Research Seminar: Nuclear envelope regulation of GTPase signalling and actomyosin activity.
15 November 2017
Dr. Derek Warren, School of Pharmacy, University of East Anglia
Tuesday 21st November, 1.00 p.m., Stacey Lecture Theatre 1
Decreased aortic compliance is an independent risk factor for the development of vascular disease. Recent studies have shown that cellular contraction contributes to aortic compliance. Vascular smooth muscle cells (VSMC) line the blood vessel wall and their contraction transiently stretches and stiffens the surrounding extracellular matrix (ECM). However, during vascular disease, VSMCs are exposed to factors that promote/deregulate their contraction, resulting in prolonged ECM stretching and stiffening. Mechanical cues derived from the ECM influence VSMC function and enhanced matrix stiffness has been shown to promote VSMC proliferation. Whether deregulated VSMC contraction during the early stages of vascular injury activates mechanotransduction to promote VSMC proliferation remains unknown. The research focus of our lab is to understand how VSMCs sense and respond to changes in their mechanical environment. In particular, we are interested in how these signals lead to changes actomyosin activity. The LInker of Nucleoskeleton and Cytoskeleton (LINC) complex forms a specialised structure that physically connects the plasma membrane, cytoskeleton and nuclear lamina to form a single, mechanically coupled system that is essential for transmission of mechanical signals across the nuclear envelope and into the nucleus. Importantly, our recent findings show that the LINC complex exists in a mechanical feedback loop with Rac1 and RhoA. We will discuss how these feedback loops influence actomyosin activity, F-actin organisation and nuclear lamina architecture in response to changes in matrix stiffness. Finally, we will discuss relationship between VSMC contraction and ECM elasticity and explore the ECM stiffness range across which VSMCs can deform the ECM and potentially influence matrix stiffness of their microenvironment.