Regulation of microtubule dynamics, mechanics and function through the growing tip

Nat Rev Mol Cell Biol. 2021 Dec;22(12):777-795. doi: 10.1038/s41580-021-00399-x. Epub 2021 Aug 18.

Abstract

Microtubule dynamics and their control are essential for the normal function and division of all eukaryotic cells. This plethora of functions is, in large part, supported by dynamic microtubule tips, which can bind to various intracellular targets, generate mechanical forces and couple with actin microfilaments. Here, we review progress in the understanding of microtubule assembly and dynamics, focusing on new information about the structure of microtubule tips. First, we discuss evidence for the widely accepted GTP cap model of microtubule dynamics. Next, we address microtubule dynamic instability in the context of structural information about assembly intermediates at microtubule tips. Three currently discussed models of microtubule assembly and dynamics are reviewed. These are considered in the context of established facts and recent data, which suggest that some long-held views must be re-evaluated. Finally, we review structural observations about the tips of microtubules in cells and describe their implications for understanding the mechanisms of microtubule regulation by associated proteins, by mechanical forces and by microtubule-targeting drugs, prominently including cancer chemotherapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Animals
  • Biomechanical Phenomena
  • Guanosine Triphosphate / metabolism
  • Humans
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / chemistry
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Microtubules / physiology*
  • Models, Biological
  • Tubulin / chemistry
  • Tubulin / metabolism
  • Tubulin Modulators / pharmacology

Substances

  • Microtubule-Associated Proteins
  • Tubulin
  • Tubulin Modulators
  • Guanosine Triphosphate