Regulation of MT dynamics via direct binding of an Abl family kinase

J Cell Biol. 2019 Dec 2;218(12):3986-3997. doi: 10.1083/jcb.201812144. Epub 2019 Nov 7.

Abstract

Abl family kinases are essential regulators of cell shape and movement. Genetic studies revealed functional interactions between Abl kinases and microtubules (MTs), but the mechanism by which Abl family kinases regulate MTs remains unclear. Here, we report that Abl2 directly binds to MTs and regulates MT behaviors. Abl2 uses its C-terminal half to bind MTs, an interaction mediated in part through electrostatic binding to tubulin C-terminal tails. Using purified proteins, we found that Abl2 binds growing MTs and promotes MT polymerization and stability. In cells, knockout of Abl2 significantly impairs MT growth, and this defect can be rescued via reexpression of Abl2. Stable reexpression of an Abl2 fragment containing the MT-binding domain alone was sufficient to restore MT growth at the cell edge. These results show Abl2 uses its C-terminal half to bind MTs and directly regulate MT dynamics.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Animals
  • Brain / metabolism
  • COS Cells
  • Cell Movement
  • Cell Shape
  • Chlorocebus aethiops
  • Cytoskeleton
  • Fibroblasts / metabolism
  • Mice
  • Microtubules / metabolism*
  • Polymerization
  • Protein Binding
  • Protein Domains
  • Protein-Tyrosine Kinases / metabolism*
  • Static Electricity
  • Swine
  • Tubulin / metabolism

Substances

  • Tubulin
  • ARG tyrosine kinase
  • Protein-Tyrosine Kinases