Lacroix et al. report that the addition of long glutamate side chains to tubulin stimulates microtubule disassembly by the microtubule-severing protein spastin.
The C-terminal tails of tubulin subunits can be modified in different ways, which might alter the recruitment of molecular motors and other microtubule-binding proteins. A family of glutamylase enzymes generates glutamate side chains of varying lengths on tubulin tails. The purpose of this modification isn't clear, though it may stimulate microtubule severing: in the protozoan Tetrahymena, blocking tubulin glutamylation has a similar effect to deleting the microtubule-severing protein katanin.
Lacroix et al. transfected HeLa cells with different glutamylases and found that enzymes that added long glutamate side chains to tubulin stimulated microtubule disassembly. The addition of shorter chains by other family members had no effect. The microtubules were disassembled by the severing protein spastin, whose activity was boosted by the polyglutamylated tubulin tails—possibly because the negatively charged glutamate residues attract a positively charged region of spastin's active site. Microtubules assembled in vitro from polyglutamylated tubulin were quickly dismantled by spastin, while non-glutamylated microtubules were more stable.
Spastin's activity is reduced by mutations associated with spastic paraplegia; defects in tubulin polyglutamylation might therefore cause neurodegeneration as well. Senior author Carsten Janke thinks that the modification facilitates microtubule cutting by spastin and katanin, but that additional signals ensure filaments are only disassembled at the right moment. He now plans to investigate how polyglutamylation affects the activity of other microtubule-interacting proteins, such as molecular motors.