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Centrosomes Control Kinetochore-Fiber Plus-End Dynamics Via HURP to Ensure Symmetric Divisions

61 Pages Posted: 6 Mar 2019 Sneak Peek Status: Review Complete

See all articles by Damian Dudka

Damian Dudka

University of Geneva - Department of Cell Physiology and Metabolism

Nicolas Liaudet

University of Geneva - Bioimaging Facility

Hélène Vassal

University of Geneva - Department of Cell Physiology and Metabolism; National Institute of Applied Sciences Lyon (INSA)

Patrick Meraldi

University of Geneva - Department of Cell Physiology and Metabolism; University of Geneva - Translational Research Centre in Onco-hematology

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Abstract

During mitosis centrosomes can affect the length of kinetochore-fibers (k-fibers) and the stability of kinetochore-microtubule attachments, implying that they regulate k-fiber dynamics. The exact cellular and molecular mechanisms by which centrosomes regulate kfibers remain, however, unknown. Here, we created human non-cancerous cells with only one centrosome to investigate these mechanisms. Such cells formed highly asymmetric bipolar spindles that resulted in asymmetric cell divisions. K-fibers in acentrosomal spindles were shorter, more stable, had a reduced poleward microtubule flux at minus-ends, and morefrequent pausing events at their plus-ends. This indicates that centrosomes regulate k-fiber dynamics both locally at minus-ends and far away at plus-ends. At the molecular level we find that the microtubule-stabilizing protein HURP is enriched on the k-fiber plus-ends in the acentrosomal spindles of cells with only one centrosome. HURP depletion rebalance k-fiber stability and dynamics in such cells, and improved spindle and cell division symmetry. Our data further indicate that HURP accumulates on k-fibers inversely proportionally to halfspindle length. We propose that centrosomes regulate k-fiber plus-ends indirectly via lengthdependent accumulation of HURP. Thus by ensuring equal k-fiber length, centrosomes promote HURP symmetry, reinforcing the symmetry of the mitotic spindle and of cell division.

Keywords: mitosis, mitotic spindle, centrosomes, plus-end k-fiber dynamics, HURP

Suggested Citation

Dudka, Damian and Liaudet, Nicolas and Vassal, Hélène and Meraldi, Patrick, Centrosomes Control Kinetochore-Fiber Plus-End Dynamics Via HURP to Ensure Symmetric Divisions (March 6, 2019). Available at SSRN: https://ssrn.com/abstract=3347763 or http://dx.doi.org/10.2139/ssrn.3347763
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Damian Dudka

University of Geneva - Department of Cell Physiology and Metabolism

102 Bd Carl-Vogt
Genève, CH - 1205
Switzerland

Nicolas Liaudet

University of Geneva - Bioimaging Facility

102 Bd Carl-Vogt
Genève, GA CH - 1205
Switzerland

Hélène Vassal

University of Geneva - Department of Cell Physiology and Metabolism

102 Bd Carl-Vogt
Genève, CH - 1205
Switzerland

National Institute of Applied Sciences Lyon (INSA)

Villeurbanne Cedex, 69621
France

Patrick Meraldi (Contact Author)

University of Geneva - Department of Cell Physiology and Metabolism ( email )

102 Bd Carl-Vogt
Genève, CH - 1205
Switzerland

University of Geneva - Translational Research Centre in Onco-hematology ( email )

102 Bd Carl-Vogt
Genève, GA CH - 1205
Switzerland

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