Microtubules and Vascular Barrier Function

Control of vascular endothelial cell barrier function results from a delicate balance between contractile and tethering forces that is significantly regulated by cross-linking of MT and actin cytoskeletal networks. Disruption of the MT network appears to set off a cascade of downstream effects on Rho-dependent mechanisms, including release of MT-bound GEFs and subsequent activation of the small GTPase Rho and Rho kinase, which ultimately results in a significant increase in MLC phosphorylation and subsequent contractile force.

Multiple factors regulate the actomyosin and MT-dependent effect on EC permeability. These include the barrier-protective effect of the cAMP-dependent protein kinase A (PKA) which likely stabilizes the MT network and retards Rho kinase activation by RhoGEFs [5].

Inflammatory cytokines such as tumor necrosis factor (TNF)-a that are secreted by macrophages and endothelial cells increase EC permeability. Presence of TNF-a also induces destabilization of microtubules. TNF-a induces MLC phosphorylation accompanied by microfilament rearrangement; however, subsequent EC permeability appears to be independent of MLCK and Rho kinase. Microtubule disassembly most likely affects TNF-a induced actin network changes and EC permeability.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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