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Mitotic Spindle Positioning (MISP) is an actin bundler that selectively stabilizes the rootlets of epithelial microvilli

E. Angelo Morales, Cayetana Arnaiz, Evan S. Krystofiak, Marija Zanic, View ORCID ProfileMatthew J. Tyska
doi: https://doi.org/10.1101/2021.08.02.454661
E. Angelo Morales
1Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA
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Cayetana Arnaiz
1Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA
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Evan S. Krystofiak
2Cell Imaging Shared Resource, Vanderbilt University, Nashville, TN 37232, USA
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Marija Zanic
1Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA
3Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN 37235, USA
4Department of Biochemistry, Vanderbilt University, Nashville, TN 37205, USA
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Matthew J. Tyska
1Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA
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  • ORCID record for Matthew J. Tyska
  • For correspondence: matthew.tyska@vanderbilt.edu
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ABSTRACT

Microvilli are conserved actin-based surface protrusions that have been repurposed throughout evolution to fulfill diverse cell functions. In the case of transporting epithelia, microvilli are supported by a core of actin filaments bundled in parallel by villin, fimbrin, and espin. Remarkably, microvilli biogenesis persists in mice lacking all three of these factors, suggesting the existence of unknown bundlers. We identified Mitotic Spindle Positioning (MISP) as an actin binding factor that localizes specifically to the rootlet end of the microvillus. MISP promotes rootlet elongation in cells, and purified MISP exhibits potent filament bundling activity in vitro. MISP-bundled filaments also recruit fimbrin, which further elongates and stabilizes bundles. MISP confinement to the rootlet is enforced by ezrin, which prevents decoration of the membrane-wrapped distal end of the core bundle. These discoveries reveal how epithelial cells optimize apical membrane surface area and offer insight on the remarkable robustness of microvilli biogenesis.

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-NC-ND 4.0 International license.
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Posted August 03, 2021.
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Mitotic Spindle Positioning (MISP) is an actin bundler that selectively stabilizes the rootlets of epithelial microvilli
E. Angelo Morales, Cayetana Arnaiz, Evan S. Krystofiak, Marija Zanic, Matthew J. Tyska
bioRxiv 2021.08.02.454661; doi: https://doi.org/10.1101/2021.08.02.454661
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Mitotic Spindle Positioning (MISP) is an actin bundler that selectively stabilizes the rootlets of epithelial microvilli
E. Angelo Morales, Cayetana Arnaiz, Evan S. Krystofiak, Marija Zanic, Matthew J. Tyska
bioRxiv 2021.08.02.454661; doi: https://doi.org/10.1101/2021.08.02.454661

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