In turn, microtubules influence actin rearrangements and cell adhesion. The centrosome nucleates a large number of dynamic microtubules, and its repositioning means that the plus ends of many of these microtubules extend into the protrusive region of the cell. Direct interactions with microtubules help guide focal adhesion dynamics in migrating cells. Microtubules might also influence actin filament formation by delivering Rac-GEFs that bind to the +TIPs traveling on growing microtubule ends. Microtubules also transport cargoes to and from the focal adhesions, thereby affecting their signaling and disassembly. Thus, microtubules reinforce the polarity information that the actin cytoskeleton receives from the outside world, allowing a sensitive response to weak signals and enabling motility to persist in the same direction for a prolonged period.
Whole-cell movements and the large-scale shaping and structuring of cells require the coordinated activities of all three basic filament systems along with a large variety of cytoskeletal accessory proteins, including motor proteins. Cell crawling—a widespread behavior important in embryonic development and also in wound healing, tissue maintenance, and immune system function in the adult animal— is a prime example of such complex, coordinated cytoskeletal action. For a cell to crawl, it must generate and maintain an overall structural polarity, which is influenced by external cues. In addition, the cell must coordinate protrusion at the leading edge (by assembly of new actin filaments), adhesion of the newly protruded part of the cell to the substratum, and forces generated by molecular motors to bring the cell body forward.
Which statements are true? Explain why or why not.
16–1 The role of ATP hydrolysis in actin polymerization is similar to the role of GTP hydrolysis in tubulin polymerization: both serve to weaken the bonds in the polymer and thereby promote depolymerization.
16–2 Motor neurons trigger action potentials in muscle cell membranes that open voltage-sensitive Ca2+ channels in T tubules, allowing extracellular Ca2+ to enter the cytosol, bind to troponin C, and initiate rapid muscle contraction.
16–3 In most animal cells, minus-end directed microtubule motors deliver their cargo to the periphery of the cell, whereas plus-end directed microtubule motors deliver their cargo to the interior of the cell.
Discuss the following problems.
16–4 The concentration of actin in cells is 50–100 times greater than the critical concentration observed for pure actin in a test tube. How is this possible? What prevents the actin subunits in cells from polymerizing into filaments? Why is it advantageous to the cell to maintain such a large pool of actin subunits?
16–5 Detailed measurements of sarcomere length and tension during isometric contraction in striated muscle provided crucial early support for the sliding-filament 2.0 2.2 1.6 1.3
I 3.6
How is the cell cortex regulated locally and globally to coordinate its activities at different places on the cell surface? What determines, for example, where filopodia form?
How are actin-regulatory proteins controlled spatially in the cytoplasm to generate multiple distinct types of actin arrays in the same cell?
Are there biologically important processes occurring inside a microtubule?
How can we account for the fact that there are many different kinesins and myosins in the cytoplasm but only one dynein?
Mutations in the nuclear lamin proteins cause a large number of diseases called laminopathies. What do we not understand about the nuclear lamina that could account for this fact?
Figure Q16–1 Tension as a function of sarcomere length during isometric contraction (Problem 16–5).