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TAOK2 is an ER-localized Kinase that Catalyzes the Dynamic Tethering of ER to Microtubules

Kimya Nourbakhsh, Amy A. Ferreccio, Matthew J. Bernard, View ORCID ProfileSmita Yadav
doi: https://doi.org/10.1101/2021.04.22.440958
Kimya Nourbakhsh
1Department of Pharmacology, University of Washington, Seattle, WA 98195
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Amy A. Ferreccio
1Department of Pharmacology, University of Washington, Seattle, WA 98195
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Matthew J. Bernard
1Department of Pharmacology, University of Washington, Seattle, WA 98195
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Smita Yadav
1Department of Pharmacology, University of Washington, Seattle, WA 98195
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  • ORCID record for Smita Yadav
  • For correspondence: smitay@uw.edu
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Summary

The endoplasmic reticulum (ER) depends on extensive association with the microtubule cytoskeleton for its structure, function and mitotic inheritance. The identity of molecular tethers that mediate ER-microtubule coupling, and mechanisms through which dynamic tethering is regulated are poorly understood. Here, we identify, Thousand And One amino acid Kinase 2 (TAOK2) as a pleiotropic protein kinase that mediates tethering of ER to microtubules. We show that TAOK2 is a unique multipass membrane spanning serine/threonine kinase localized in distinct ER domains via four transmembrane and amphipathic helices. Using in vitro and cellular assays, we find that TAOK2 directly binds microtubules with high affinity. We define the minimal TAOK2 determinants that induce ER-microtubule tethering, and delineate the mechanism for its autoregulation. While ER membrane dynamics are increased in TAOK2 knockout cells, the movement of ER along growing microtubule plus-ends is disrupted. We show that ER-microtubule tethering is tightly regulated by catalytic activity of TAOK2 in both interphase and mitotic cells, perturbation of which leads to profound defects in ER morphology and cell division. Our study identifies TAOK2 as an ER-microtubule tether, and reveals a kinase-regulated mechanism for control of ER dynamics critical for cell growth and division.

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 April 22, 2021.
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TAOK2 is an ER-localized Kinase that Catalyzes the Dynamic Tethering of ER to Microtubules
Kimya Nourbakhsh, Amy A. Ferreccio, Matthew J. Bernard, Smita Yadav
bioRxiv 2021.04.22.440958; doi: https://doi.org/10.1101/2021.04.22.440958
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TAOK2 is an ER-localized Kinase that Catalyzes the Dynamic Tethering of ER to Microtubules
Kimya Nourbakhsh, Amy A. Ferreccio, Matthew J. Bernard, Smita Yadav
bioRxiv 2021.04.22.440958; doi: https://doi.org/10.1101/2021.04.22.440958

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