Preprint Review Version 1 This version is not peer-reviewed

How Essential Kinesin-5 Becomes Non-Essential: Force Balance and Microtubule Dynamics Matter

Version 1 : Received: 20 April 2020 / Approved: 21 April 2020 / Online: 21 April 2020 (05:58:17 CEST)

A peer-reviewed article of this Preprint also exists.

Yukawa, M.; Teratani, Y.; Toda, T. How Essential Kinesin-5 Becomes Non-Essential in Fission Yeast: Force Balance and Microtubule Dynamics Matter. Cells 2020, 9, 1154. Yukawa, M.; Teratani, Y.; Toda, T. How Essential Kinesin-5 Becomes Non-Essential in Fission Yeast: Force Balance and Microtubule Dynamics Matter. Cells 2020, 9, 1154.

Journal reference: Cells 2020, 9, 1154
DOI: 10.3390/cells9051154

Abstract

The bipolar mitotic spindle drives accurate chromosome segregation by capturing the kinetochore and pulling each set of sister chromatids to the opposite poles. In this review, we describe recent findings on the multiple pathways leading to bipolar spindle formation in fission yeast and discuss these results from a broader perspective. Roles of four mitotic kinesins (Kinesin-5, Kinesin-6, Kinesin-12 and Kinesin-14) in spindle assembly are depicted, and how a group of microtubule-associated proteins, sister chromatid cohesion and the kinetochore collaborates with these motors is shown. We have paid special attention to the molecular pathways that render otherwise essential Kinesin-5 to become non-essential: how cells build bipolar mitotic spindles without the need for Kinesin-5 and where the alternate forces come from are considered. We highlight the force balance for bipolar spindle assembly and explain how outward and inward forces are generated by various ways, in which the proper fine-tuning of microtubule dynamics plays a crucial role. Overall, these new pathways have illuminated remarkable plasticity and adaptability of spindle mechanics. Kinesin molecules are regarded as prospective targets for cancer chemotherapy and many specific inhibitors have been developed. However, several hurdles have arisen against their clinical implementation. This review provides insight into possible strategies to overcome these challenges.

Subject Areas

bipolar mitotic spindle; fission yeast; kinesin; kinetochore; microtubule dynamics; microtubule polymerase; microtubule–associated proteins (MAPs); spindle pole body (SPB); sister chromatid cohesion

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