Katanin activity in tau envelopes negatively correlates with ATP levels.

Abstract

Katanin is an ATP-dependent microtubule severing enzyme involved in neuronal development and function. Neurodegeneration-related protein tau cooperatively forms dense envelopes on microtubules. These envelopes can protect the microtubule lattice from katanin-induced microtubule disassembly. Neurodegenerative processes and aging are accompanied by changes in the level of intracellular ATP, however, how is katanin-tau interplay regulated by ATP level is unclear. Here we show that in presence of katanin, ATP decrease causes enhanced disassembly of tau envelope-coated microtubules. Performing katanin-driven severing experiments at 3 and 10 mM ATP, we found that katanin ATP-ase activity on bare microtubules was identical. However, counterintuitively, in presence of tau envelopes, katanin severed microtubules significantly faster in the presence of 3 mM ATP compared to the increased ATP level. These results suggest that the protective function of tau envelopes is ATP-dependent, and links decreased ATP levels with microtubule disassembly.