Augmin-dependent microtubule self-organization drives kinetochore fiber maturation in mammals

Almeida, AC; Soares-de-Oliveira, J; Drpic, D; Cheeseman, LP; Damas, J; Lewin, HA; Larkin, DM; Aguiar, P; Pereira, AJ; Maiato, H

Abstract

Chromosome segregation in mammals relies on the maturation of a thick bundle of kinetochore-attached microtubules known as k-fiber. How k-fibers mature from initial kinetochore microtubule attachments remains a fundamental question. By combining molecular perturbations and phenotypic analyses in Indian muntjac fibroblasts containing the lowest known diploid chromosome number in mammals (2N = 6) and distinctively large kinetochores, with fixed/live-cell super-resolution coherent-hybrid stimulated emission depletion (CH-STED) nanoscopy and laser microsurgery, we demonstrate a key role for augmin in kinetochore micro tubule self-organization and maturation, regardless of pioneer centrosomal microtubules. In doing so, augmin promotes kinetochore and interpolar microtubule turnover and poleward flux. Tracking of microtubule growth events within individual k-fibers reveals a wide angular dispersion, consistent with augmin-mediated branched microtubule nucleation. Augmin depletion reduces the frequency of kinetochore microtubule growth events and hampers efficient repair after acute k-fiber injury by laser microsurgery. Together, these findings underscore the contribution of augmin-mediated microtubule amplification for k-fiber self -organization and maturation in mammals.

Citation

Almeida, A., Soares-de-Oliveira, J., Drpic, D., Cheeseman, L., Damas, J., Lewin, H., Larkin, D., Aguiar, P., Pereira, A., & Maiato, H. (2022). Augmin-dependent microtubule self-organization drives kinetochore fiber maturation in mammals. Cell Reports, 39(1), https://doi.org/10.1016/j.celrep.2022.110610

• Journal Article Type: Article
• Acceptance Date: Mar 11, 2022
• Publication Date: Apr 5, 2022
• Deposit Date: Aug 23, 2022
• Publicly Available Date: Aug 23, 2022
• Journal: Cell Reports
• Print ISSN: 2211-1247
• Publisher: Cell Press
• Peer Reviewed: Peer Reviewed
• Volume: 39
• Issue: 1
• DOI: https://doi.org/10.1016/j.celrep.2022.110610
• Keywords: MITOTIC-SPINDLE; INDIAN MUNTJAC; CHROMOSOME CONGRESSION; ALPHA-TUBULIN; LIVE-CELL; COMPLEX; NUCLEATION; DETYROSINATION; CONTRIBUTES; COMPONENT