2. Academic Validation
  3. Microtubule nucleation from the fibrous corona by LIC1-pericentrin promotes chromosome congression

Microtubule nucleation from the fibrous corona by LIC1-pericentrin promotes chromosome congression

  • Curr Biol. 2023 Jan 24;S0960-9822(23)00010-6. doi: 10.1016/j.cub.2023.01.010.
Jingchao Wu 1,  Ainhoa Larreategui-Aparicio 2,  Maaike L A Lambers 1,  Dani L Bodor 1,  Sjoerd J Klaasen 1,  Eveline Tollenaar 3,  Marta de Ruijter-Villani 4,  Geert J P L Kops 5
Affiliations

Affiliations

  • 1 Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), Uppsalalaan 8, 3584CT Utrecht, the Netherlands; University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, the Netherlands; Oncode Institute, Jaarbeursplein 6, 3521AL Utrecht, the Netherlands.
  • 2 Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), Uppsalalaan 8, 3584CT Utrecht, the Netherlands; University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, the Netherlands; Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584CL Utrecht, the Netherlands.
  • 3 Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584CL Utrecht, the Netherlands.
  • 4 Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), Uppsalalaan 8, 3584CT Utrecht, the Netherlands; University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, the Netherlands; Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584CL Utrecht, the Netherlands; Division of Woman and Baby, Department of Obstetrics and Gynecology, University Medical Centre Utrecht, Heidelberglaan 100, 3584CX Utrecht, the Netherlands.
  • 5 Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), Uppsalalaan 8, 3584CT Utrecht, the Netherlands; University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, the Netherlands; Oncode Institute, Jaarbeursplein 6, 3521AL Utrecht, the Netherlands. Electronic address: g.kops@hubrecht.eu.
PMID: 36720222 DOI: 10.1016/j.cub.2023.01.010
Abstract

Error-free chromosome segregation in mitosis and meiosis relies on the assembly of a microtubule-based spindle that interacts with kinetochores to guide chromosomes to the cell equator before segregation in anaphase. Microtubules sprout from nucleation sites such as centrosomes, but kinetochores can also promote microtubule formation. It is unclear, however, how kinetochore-derived microtubules are generated and what their role is in chromosome segregation. Here, we show that the transient outer-kinetochore meshwork known as the fibrous corona serves as an autonomous microtubule nucleation platform. The fibrous corona is essential for the nucleation of kinetochore-derived microtubules, and when dissociated from the core kinetochore, it retains microtubule nucleation capacity. Nucleation relies on a fibrous-corona-bound pool of the LIC1 subunit of the dynein motor complex, which interacts with the γ-tubulin-tethering protein pericentrin (PCNT). PCNT is essential for microtubule nucleation from fibrous coronas, and in centrosome-depleted cells, where nearly all mitotic nucleation occurs at fibrous coronas, chromosome congression is fully dependent on PCNT. We further show that chromosomes in bovine oocytes, which naturally lack centrosomes, have highly expanded fibrous coronas that drive chromosome-derived microtubule nucleation. Preventing fibrous corona expansion in these cells impairs chromosome congression and causes spindle assembly defects. Our results show that fibrous coronas are autonomous microtubule-organizing centers that are important for spindle assembly, which may be especially relevant in acentrosomal cells such as oocytes.

Keywords

cell division; chromosome; fibrous corona; kinetochore; meiosis; microtubule; microtubule nucleation; mitosis; oocyte; pericentrin.

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