Severing saves microtubules

Mutations in Spastin are associated with Hereditary Spastic Paraplegia (HSP), a disease characterized by retrograde axonal degeneration and a spastic gait. On page 599, Evans et al. demonstrate that Spastin is a microtubule-severing protein. The result leaves an unresolved paradox: how can the loss of a microtubule-severing protein result in shorter microtubule fibers?

Spastin is a member of the AAA ATPase protein family, and thus has a highly conserved ATP-binding domain. Within the family, Spastin is most like Katanin, a microtubule-severing protein required for the function of worm meiosis and rodent neurons. Spastin overexpression decreases the number of microtubules in cells, suggesting that it too might cut microtubules.

The team generated point mutations that disrupted ATP binding or hydrolysis. ATP binding was required for Spastin association with microtubules,...