Microtubules (MTs) are cylindrical polymeric 25-nm tubes composed of parallel bundles of 13 linear protofilaments made up of a/p tubulin heterodimers. Uniform orientation of the protofilaments within the tubule conveys polarity to the entire microtubule. Microtubules continually undergo cyclic polymerization and depolymerization, known as dynamic instability. Post-translational modifications of tubulin molecules, such as acetylation and detyrosi-nation, as well as capping of the microtubules' plus ends, are thought to stabilize and mature microtubules. Microtubules have critically important roles in mitosis, cell migration, and intracellular transport of a large number of proteins and organelles via microtubule-associated proteins (MAPs).
Multiple aspects of endothelial cell motility, including migration, morphological changes, and proliferation as well as control of endothelial cell intracellular tension and contractility, involve cross-linking between the MT and actin microfilament networks. Microtubule distribution and dynamic instability regulate the activity of small GTPase-mediated signal transduction cascades that control microfilament network dynamics due in part to nonmotor MAPs known as MT-associated guanine-nucleotide exchange factors (GEFs), a family of proteins that regulate activity of Rho GTPases. Furthermore, MT depolymeriza-tion results in activation of Rho, stress fiber formation and apoptosis. Inversely, multiple signaling molecules associate with MT and may regulate MT dynamics including Rac1, proteins upstream of Rac1, and mDia1 . It is clear that microtubule distribution and state of assembly/disassembly has a significant impact on the state of endothelial cell intra-cellular tension and contractility.
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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.