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Competition between myosin II and βH-Spectrin regulates cytoskeletal tension

View ORCID ProfileConsuelo Ibar, View ORCID ProfileKrishna Chinthalapudi, Sarah M. Heissler, View ORCID ProfileKenneth D. Irvine
doi: https://doi.org/10.1101/2022.12.01.518662
Consuelo Ibar
1Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway NJ 08854 USA
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Krishna Chinthalapudi
2Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, Ohio, USA
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Sarah M. Heissler
2Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, Ohio, USA
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Kenneth D. Irvine
1Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway NJ 08854 USA
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  • For correspondence: irvine@waksman.rutgers.edu
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ABSTRACT

Spectrins are membrane cytoskeletal proteins generally thought to function as heterotetramers comprising two α-spectrins and two β-spectrins. They influence cell shape and Hippo signaling, but the mechanism by which they influence Hippo signaling has remained unclear. We have investigated the role and regulation of the Drosophila β-heavy Spectrin (βH-Spectrin, encoded by the karst gene) in wing imaginal discs. Our results establish that βH-Spectrin regulates Hippo signaling through the Jub biomechanical pathway due to its influence on cytoskeletal tension. While we find that α-Spectrin also regulates Hippo signaling through Jub, unexpectedly, we find that βH-Spectrin localizes and functions independently of α-Spectrin. Instead, βH-Spectrin co-localizes with and reciprocally regulates and is regulated by myosin. In vivo and in vitro experiments support a model in which βH-Spectrin and myosin directly compete for binding to apical F-actin. This competition can explain the influence of βH-Spectrin on cytoskeletal tension and myosin accumulation. It also provides new insight into how βH-Spectrin participates in ratcheting mechanisms associated with cell shape change.

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 4.0 International license.
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Posted December 01, 2022.
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Competition between myosin II and βH-Spectrin regulates cytoskeletal tension
Consuelo Ibar, Krishna Chinthalapudi, Sarah M. Heissler, Kenneth D. Irvine
bioRxiv 2022.12.01.518662; doi: https://doi.org/10.1101/2022.12.01.518662
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Competition between myosin II and βH-Spectrin regulates cytoskeletal tension
Consuelo Ibar, Krishna Chinthalapudi, Sarah M. Heissler, Kenneth D. Irvine
bioRxiv 2022.12.01.518662; doi: https://doi.org/10.1101/2022.12.01.518662

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