Abstract
Microtubules are dynamic cytoskeletal filaments composed of αβ-tubulin heterodimers. Historically, the dynamics of single tubulin interactions at the growing microtubule tip have been inferred from steady-state growth kinetics. However, recent advances in the production of recombinant tubulin and in high-resolution optical and cryo-electron microscopies have opened new windows into understanding the impacts of specific intermolecular interactions during growth. The microtubule lattice is held together by lateral and longitudinal tubulin-tubulin interactions, and these interactions are in turn regulated by the GTP hydrolysis state of the tubulin heterodimer. Furthermore, tubulin can exist in either an extended or a compacted state in the lattice. Growing evidence has led to the suggestion that binding of microtubule-associated proteins (MAPs) or motors can induce changes in tubulin conformation and that this information can be communicated through the microtubule lattice. Progress in understanding how dynamic tubulin-tubulin interactions control dynamic instability has benefitted from visualizing structures of growing microtubule plus ends and through stochastic biochemical models constrained by experimental data. Here, we review recent insights into the molecular basis of microtubule growth and discuss how MAPs and regulatory proteins alter tubulin-tubulin interactions to exert their effects on microtubule growth and stability.