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

Summary: 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 analys...

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Main Authors: Ana C. Almeida, Joana Soares-de-Oliveira, Danica Drpic, Liam P. Cheeseman, Joana Damas, Harris A. Lewin, Denis M. Larkin, Paulo Aguiar, António J. Pereira, Helder Maiato
Format: Article
Language:English
Published: Elsevier 2022-04-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124722003588
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author Ana C. Almeida
Joana Soares-de-Oliveira
Danica Drpic
Liam P. Cheeseman
Joana Damas
Harris A. Lewin
Denis M. Larkin
Paulo Aguiar
António J. Pereira
Helder Maiato
author_facet Ana C. Almeida
Joana Soares-de-Oliveira
Danica Drpic
Liam P. Cheeseman
Joana Damas
Harris A. Lewin
Denis M. Larkin
Paulo Aguiar
António J. Pereira
Helder Maiato
author_sort Ana C. Almeida
collection DOAJ
description Summary: 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 microtubule 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.
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spelling doaj.art-c40ca0a195364fde9978aa9ef1f9d79c2022-12-21T19:20:54ZengElsevierCell Reports2211-12472022-04-01391110610Augmin-dependent microtubule self-organization drives kinetochore fiber maturation in mammalsAna C. Almeida0Joana Soares-de-Oliveira1Danica Drpic2Liam P. Cheeseman3Joana Damas4Harris A. Lewin5Denis M. Larkin6Paulo Aguiar7António J. Pereira8Helder Maiato9Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, PortugalDepartment of Comparative Biomedical Sciences, Royal Veterinary College, University of London, London NW1 0TU, UK; Department of Evolution and Ecology, University of California, Davis, CA 95616, USADepartment of Evolution and Ecology, University of California, Davis, CA 95616, USADepartment of Comparative Biomedical Sciences, Royal Veterinary College, University of London, London NW1 0TU, UKInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; Instituto Nacional de Engenharia Biomédica (INEB), Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; Cell Division Group, Department of Biomedicine, Faculdade de Medicina, Universidade do Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal; Corresponding authorSummary: 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 microtubule 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.http://www.sciencedirect.com/science/article/pii/S2211124722003588CP: Cell biology
spellingShingle Ana C. Almeida
Joana Soares-de-Oliveira
Danica Drpic
Liam P. Cheeseman
Joana Damas
Harris A. Lewin
Denis M. Larkin
Paulo Aguiar
António J. Pereira
Helder Maiato
Augmin-dependent microtubule self-organization drives kinetochore fiber maturation in mammals
Cell Reports
CP: Cell biology
title Augmin-dependent microtubule self-organization drives kinetochore fiber maturation in mammals
title_full Augmin-dependent microtubule self-organization drives kinetochore fiber maturation in mammals
title_fullStr Augmin-dependent microtubule self-organization drives kinetochore fiber maturation in mammals
title_full_unstemmed Augmin-dependent microtubule self-organization drives kinetochore fiber maturation in mammals
title_short Augmin-dependent microtubule self-organization drives kinetochore fiber maturation in mammals
title_sort augmin dependent microtubule self organization drives kinetochore fiber maturation in mammals
topic CP: Cell biology
url http://www.sciencedirect.com/science/article/pii/S2211124722003588
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