L’équipe Pintard a publié un nouvel article dans The Journal of Cell biology :
Intramolecular regulation of the MT-severing enzyme Katanin prevents futile ATP hydrolysis
Résumé :
Microtubule-severing enzymes are evolutionarily conserved AAA-ATPases that sever microtubules, thereby regulating diverse microtubule-dependent cellular processes. How these enzymes couple Microtubule binding with ATP hydrolysis to trigger microtubule-remodeling remains poorly understood. Using Caenorhabditiselegans Katanin, which contains the MEI-1 catalytic AAA+ p60 and MEI-2 p80-like regulatory subunits, we identify a critical regulatory role of the N-terminal domain of MEI-1 in Katanin regulation. We demonstrate this domain represses the AAA+ core in cis, limiting ATP hydrolysis and preventing interaction with tubulin C-terminal tails in the absence of MEI-2. Strikingly, MEI-1 lacking its N terminus is constitutively active, enabling identification of pore residues critical for sensing microtubule C-terminal tails and relaying this signal to the AAA+ core. These findings reveal how Katanin activation is coupled to microtubule binding, thereby avoiding futile ATP hydrolysis. Given Katanin’s evolutionary conservation, our work provides a mechanistic framework for its regulation in other organisms, with broader implications for human pathologies, including neurodegeneration and cancer.
Joly N, Pintard L. Intramolecular regulation of the MT-severing enzyme Katanin prevents futile ATP hydrolysis. J Cell Biol. 2026 Feb 2;225(2):e202506192. doi: 10.1083/jcb.202506192. Epub 2025 Nov 19. PMID: 41258800.