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bioRxiv · 10.1101/2022.12.01.518662

Competition between myosin II and βH-Spectrin regulates cytoskeletal tension

Ibar, C.·Chinthalapudi, K.·Heissler, S.·Irvine, K. D.
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Abstract

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

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Ibar, C., Chinthalapudi, K., Heissler, S., Irvine, K. D.. 2022-12-01. Competition between myosin II and βH-Spectrin regulates cytoskeletal tension. https://doi.org/10.1101/2022.12.01.518662

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