Microtubule amplification in the assembly of mitotic spindle and the maturation of kinetochore fibers

Abstract

Efficient assembly of a mitotic spindle and stable attachment of microtubules (k-fibers) to kinetochores are essential for the high fidelity of chromosome segregation. Both spindle assembly and k-fiber formation require robust nucleation and polymerization of microtubules mediated by the γ-tubulin ring complex (γTuRC). It has been well established that centrosomes and chromatin are the two centers for microtubule nucleation. We recently demonstrate a third mechanism for microtubule nucleation and polymerization, in which the existing microtubules in the spindle act as templates to promote the formation of new microtubules. We showed that a novel spindle-associated protein, FAM29A, plays a critical role in this microtubule-dependent microtubule amplification. FAM29A associates with spindle microtubules and directly interacts with and recruits NEDD1, the targeting subunit of γTuRC. Spindleassociated γTuRC then promotes microtubule nucleation required for spindle assembly and k-fiber formation. This novel microtubule amplification pathway provides a powerful mechanism to control the local cytoskeleton structures independent of centrosomes and chromatin. We speculate that microtubule amplification not only functions in mitosis, but may also act in other physiological processes to re-enforce existing cytoskeleton structures. ©2009 Landes Biosciences.