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Differential Regulation of Single Microtubules and Bundles by a Three-Protein Module

Nandini Mani, Shuo Jiang, Alex E. Neary, Sithara S. Wijeratne, Radhika Subramanian
doi: https://doi.org/10.1101/2020.03.05.979864
Nandini Mani
1Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
2Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
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Shuo Jiang
1Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
2Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
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Alex E. Neary
1Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
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Sithara S. Wijeratne
1Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
2Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
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Radhika Subramanian
1Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
2Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
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  • For correspondence: radhika@molbio.mgh.harvard.edu
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ABSTRACT

A remarkable feature of the microtubule cytoskeleton is co-existence of sub-populations having different dynamic properties. A prominent example is the anaphase spindle, where stable antiparallel bundles exist alongside dynamic microtubules and provide spatial cues for cytokinesis. How are dynamics of spatially proximal arrays differentially regulated? We reconstitute a minimal system of three midzone proteins: microtubule-crosslinker PRC1, and its interactors CLASP1 and Kif4A, proteins that promote and suppress microtubule elongation, respectively. We find their collective activity promotes elongation of single microtubules, while simultaneously stalling polymerization of crosslinked bundles. This differentiation arises from (i) Strong rescue activity of CLASP1, which overcomes weaker effects of Kif4A on single microtubules, (ii) Lower microtubule and PRC1-binding affinity of CLASP1, which permit dominance of Kif4A at overlaps. In addition to canonical mechanisms where antagonistic regulators set microtubule lengths, our findings illuminate design principles by which collective regulator activity creates microenvironments of arrays with distinct dynamic properties.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted April 08, 2021.
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Differential Regulation of Single Microtubules and Bundles by a Three-Protein Module
Nandini Mani, Shuo Jiang, Alex E. Neary, Sithara S. Wijeratne, Radhika Subramanian
bioRxiv 2020.03.05.979864; doi: https://doi.org/10.1101/2020.03.05.979864
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Differential Regulation of Single Microtubules and Bundles by a Three-Protein Module
Nandini Mani, Shuo Jiang, Alex E. Neary, Sithara S. Wijeratne, Radhika Subramanian
bioRxiv 2020.03.05.979864; doi: https://doi.org/10.1101/2020.03.05.979864

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