Journal
JOURNAL OF CELL SCIENCE
Volume 129, Issue 7, Pages 1319-1328Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.178806
Keywords
Dynamic instability; Microtubule; Microtubule-associated protein; Mitosis
Categories
Funding
- Pew Charitable Trusts through Pew Scholars Program in Biomedical Sciences
- National Institutes of Health [NIGMS GM-103833]
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TPX2 is a widely conserved microtubule-associated protein that is required for mitotic spindle formation and function. Previous studies have demonstrated that TPX2 is required for the nucleation of microtubules around chromosomes; however, the molecular mechanism by which TPX2 promotes microtubule nucleation remains a mystery. In this study, we found that TPX2 acts to suppress tubulin subunit off-rates during microtubule assembly and disassembly, thus allowing for the support of unprecedentedly slow rates of plus-end microtubule growth, and also leading to a dramatically reduced microtubule shortening rate. These changes in microtubule dynamics can be explained in computational simulations by a moderate increase in tubulin-tubulin bond strength upon TPX2 association with the microtubule lattice, which in turn acts to reduce the departure rate of tubulin subunits from the microtubule ends. Thus, the direct suppression of tubulin subunit off-rates by TPX2 during microtubule growth and shortening could provide a molecular mechanism to explain the nucleation of new microtubules in the presence of TPX2.
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