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Severing enzymes amplify microtubule arrays through lattice GTP-tubulin incorporation

TitleSevering enzymes amplify microtubule arrays through lattice GTP-tubulin incorporation
Publication TypeJournal Article
Year of Publication2018
AuthorsVemu, A, Szczesna E, Zehr EA, Spector JO, Grigorieff N, Deaconescu AM, Roll-Mecak A
Refereed DesignationRefereed
JournalScience
Volume361
Issue6404
Date Published2018 08 24
ISSN1095-9203
Abstract

Spastin and katanin sever and destabilize microtubules. Paradoxically, despite their destructive activity they increase microtubule mass in vivo. We combined single-molecule total internal reflection fluorescence microscopy and electron microscopy to show that the elemental step in microtubule severing is the generation of nanoscale damage throughout the microtubule by active extraction of tubulin heterodimers. These damage sites are repaired spontaneously by guanosine triphosphate (GTP)-tubulin incorporation, which rejuvenates and stabilizes the microtubule shaft. Consequently, spastin and katanin increase microtubule rescue rates. Furthermore, newly severed ends emerge with a high density of GTP-tubulin that protects them against depolymerization. The stabilization of the newly severed plus ends and the higher rescue frequency synergize to amplify microtubule number and mass. Thus, severing enzymes regulate microtubule architecture and dynamics by promoting GTP-tubulin incorporation within the microtubule shaft.

URLhttp://science.sciencemag.org/content/361/6404/eaau1504
DOI10.1126/science.aau1504
Alternate JournalScience
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