Changes in microtubule overlap length regulate kinesin-14-driven microtubule sliding

Marcus Braun, Zdenek Lansky, Agata Szuba, Friedrich W. Schwarz, Aniruddha Mitra, Mengfei Gao, Annemarie Lüdecke, Pieter Rein Ten Wolde, Stefan Diez

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Microtubule-crosslinking motor proteins, which slide antiparallel microtubules, are required for the remodeling of microtubule networks. Hitherto, all microtubule-crosslinking motors have been shown to slide microtubules at a constant velocity until no overlap remains between them, leading to the breakdown of the initial microtubule geometry. Here, we show in vitro that the sliding velocity of microtubules, driven by human kinesin-14 HSET, decreases when microtubules start to slide apart, resulting in the maintenance of finite-length microtubule overlaps. We quantitatively explain this feedback using the local interaction kinetics of HSET with overlapping microtubules that cause retention of HSET in shortening overlaps. Consequently, the increased HSET density in the overlaps leads to a density-dependent decrease in sliding velocity and the generation of an entropic force that antagonizes the force exerted by the motors. Our results demonstrate that a spatial arrangement of microtubules can regulate the collective action of molecular motors through the local alteration of their individual interaction kinetics.
Original languageEnglish
Pages (from-to)1245-1252
Number of pages8
JournalNature Chemical Biology
Issue number12
Early online date16 Oct 2017
Publication statusPublished - 1 Dec 2017


We thank the members of the Diez laboratory for fruitful discussions, C. Walczak for the HSET plasmid DNA used as PCR template, G. Fink for helping to initiate the project and F. Ruhnow for generating the simulation kymographs. We acknowledge the financial support from the European Research Council (ERC starting grant 242933 to S.D.), the Deutsche Forschungsgemeinschaft (Heisenberg program grant DI 1226/4 and research unit SFG 877 grant DI 1226/5), the Czech Science Foundation (grant no. 15-17488S to Z.L. and 17-12496Y to M.B.), the Introduction of New Research Methods to BIOCEV (CZ.1.05/2.1.00/19.0390) project from the ERDF and institutional support from the Institute of Biotechnology RVO: 86652036. This work is part of the research program of the Foundation for Fundamental Research on Matter (FOM), which is part of the Netherlands Organization for Scientific Research (NWO).

FundersFunder number
Institute of Biotechnology RVO86652036
Netherlands Organization for Scientific Research
Seventh Framework Programme242933
European Research Council
Deutsche ForschungsgemeinschaftDI 1226/4, DI 1226/5
Grantová Agentura České Republiky15-17488S, 17-12496Y, CZ.1.05/2.1.00/19.0390
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Foundation for Fundamental Research on Matter
European Regional Development Fund


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