Regulation of Microtubule Dynamics Signaling Pathway
Microtubules are required for the establishment of cell polarity, polarized migration of cells, intracellular vesicle transport, and chromosomal segregation in mitosis. Microtubules (MTs) are nonequilibrium polymers of α/β-tubulin heterodimers, in which GTP hydrolysis on the β-tubulin subunit occurs following assembly. Most microtubules are nucleated from organizing centers. The most prevalent microtubule behavior is dynamic instability, a process of slow plus end growth coupled with rapid depolymerization (“catastrophe”) and subsequent rescue. Although microtubule minus ends show dynamic instability, albeit at a lower rate than the plus ends, the minus ends are usually capped and anchored at MT organizing centers and thus often do not participate in microtubule dynamics.
Maintaining a balance between dynamically unstable and stable microtubules is regulated in large part by proteins that bind either tubulin dimers or assembled microtubules. Proteins that bind tubulin dimers include stathmin, which sequesters tubulin and enhances MT dynamics by increasing catastrophe frequency, and collapsin response mediator protein (CRMP2), which increases MT growth rate by promoting addition of tubulin dimers onto microtubule plus ends. Other proteins that associate with assembled MTs include those that bundle MTs (e.g. MAP1c), those that stabilize MTs (e.g. tau), and those that maintain MTs in a dynamic state (MAP1b). A major signaling pathway that regulates MT dynamics involves GSK-3β, a kinase typically active under basal growth conditions but locally inactive in response to signals that enhance MT growth and dynamics.
Tubulin undergoes several post-translational modifications such as acetylation, polyglutamylation, and poly-glycylation, which have been shown to alter the association with certain MT motors as well as other proteins that can affect MT stability and dynamics.
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We would like to thank Prof. James Bamburg, Colorado State University, Fort Collins, CO for updates to the Regulation of Actin Dynamics and the Regulation of Microtubule Dynamics pathways.
created September 2008
revised September 2012