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

被引:12
作者
Almeida, Ana C. [1 ,2 ]
Soares-de-Oliveira, Joana [1 ,2 ]
Drpic, Danica [1 ,2 ,7 ]
Cheeseman, Liam P. [1 ,2 ]
Damas, Joana [3 ,4 ]
Lewin, Harris A. [4 ]
Larkin, Denis M. [3 ]
Aguiar, Paulo [1 ,5 ]
Pereira, Antonio J. [1 ,2 ]
Maiato, Helder [1 ,2 ,6 ]
机构
[1] Univ Porto, Inst Invest & Inovacao Saude I3S, Rua Alfredo Allen 208, P-4200135 Porto, Portugal
[2] Univ Porto, Inst Biol Mol & Celular, Rua Alfredo Allen 208, P-4200135 Porto, Portugal
[3] Univ London, Royal Vet Coll, Dept Comparat Biomed Sci, London NW1 0TU, England
[4] Univ Calif Davis, Dept Evolut & Ecol, Davis, CA 95616 USA
[5] Univ Porto, Inst Nacl Engn Biomed INEB, Rua Alfredo Allen 208, P-4200135 Porto, Portugal
[6] Univ Porto, Fac Med, Dept Biomed, Cell Div Grp, Alameda Prof Hernani Monteiro, P-4200319 Porto, Portugal
[7] Austrian Acad Sci, Res Ctr Mol Med, CeM, Lazarettgasse 14, A-1090 Vienna, Austria
来源
CELL REPORTS | 2022年 / 39卷 / 01期
基金
欧洲研究理事会;
关键词
MITOTIC-SPINDLE; INDIAN MUNTJAC; CHROMOSOME CONGRESSION; ALPHA-TUBULIN; LIVE-CELL; COMPLEX; NUCLEATION; DETYROSINATION; CONTRIBUTES; COMPONENT;
D O I
10.1016/j.celrep.2022.110610
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页数:27
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