76 - The Endothelial Cytoskeleton

Summary

The vascular endothelium represents an enormous and heterogeneous organ faced with diverse challenges. The individual endothelial cells (ECs) that make up this organ must organize a polarized and discrete monolayer, with a range of tissue specific specializations. The endothelium must be capable of carefully balancing and dynamically regulating both barrier function and selective permeability to solutes and immune cells. ECs must resist significant, and in some settings extreme, mechanical forces including fluid shear, hydrostatic pressure, and cyclical stretch. Finally, these cells must be able to efficiently migrate and, indeed, invade tissue matrices during the formation of new vessels. The cytoskeleton of the endothelium is central to meeting all these challenges. Our growing knowledge of the roles and regulation of cytoskeletal components in endothelium provides us with an improved understanding of endothelial function in both health and disease.

AN OVERVIEW OF THE CYTOSKELETON

The cytoskeleton is formed by three kinds of protein filaments, which together provide cells with shape, mechanical strength, spatial organization/polarity, and movement. They also serve to connect protein complexes and organelles in distinct parts of the cell, and can provide tracks for transport between them. These filaments include microfilaments (or “actin filaments”), microtubules, and intermediate filaments. Each of these is formed by the polymerization of separate sets of proteins with distinct dynamics and stability. The dynamics, stability, and function of these filaments are highly dependent on a large repertoire of accessory and regulatory proteins that control the localized assembly, connect filaments to each other and other cellular components, and provide motors that move organelles (or other filaments) along their length.