The microtubule GTP-tubulin cap size is modulated during cell division

Microtubule dynamics change during cell division to enable rapid microtubule network remodeling. The switching from microtubule growth to shrinkage is attributed to the loss of a stabilizing GTP-cap structure at the growing microtubule end. The size of the GTP-cap is a result of a balance between GTP-tubulin addition to the microtubule end and subsequent GTP-hydrolysis in the microtubule lattice. Whether the cell-cycle-dependent changes in microtubule dynamics are supported by concurrent modulation of the stabilizing GTP-cap size is not known. Here, we use high spatiotemporal resolution live-cell imaging of EB1, an established marker for the GTP-cap, to directly determine the relationship between GTP-cap size and microtubule growth rate throughout the cell cycle. Our data reveal that GTP-cap size for matching growth rates is reduced during mitosis. Comparison of EB1 comets on astral versus spindle microtubules reveals that the scaling between the GTP-cap size and microtubule growth rate is not spatially regulated in mitosis. We find that these regulatory patterns are conserved across epithelial cells from two different species. Taken together, our findings reveal modulation of GTP-cap size as a cell-cycle-regulated mechanism for tuning microtubule stability. Significance StatementMicrotubule dynamics are altered during the cell cycle to enable rapid microtubule network remodeling and accurate chromosome segregation. By comparing EB1 comets on microtubule ends during different cell cycle stages, the authors find that microtubule GTP-cap size is subject to global differential regulation during specific cell cycle stages. These results identify modulation of microtubule stabilizing GTP-cap size as a previously underappreciated, cell-cycle-regulated mechanism for tuning microtubule stability throughout the cell cycle.