Competition between myosin II and β<sub>H</sub>-spectrin regulates cytoskeletal tension.

Ibar, Consuelo; Chinthalapudi, Krishna; Heissler, Sarah M; Irvine, Kenneth D · Elife · 2023

basic_science · Level V

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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 <i>Drosophila</i> β-heavy spectrin (β<sub>H</sub>-spectrin, encoded by the <i>karst</i> gene) in wing imaginal discs. Our results establish that β<sub>H</sub>-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 β<sub>H</sub>-spectrin localizes and functions independently of α-spectrin. Instead, β<sub>H</sub>-spectrin co-localizes with and reciprocally regulates and is regulated by myosin. <i>In vivo</i> and <i>in vitro</i> experiments support a model in which β<sub>H</sub>-spectrin and myosin directly compete for binding to apical F-actin. This competition can explain the influence of β<sub>H</sub>-spectrin on cytoskeletal tension and myosin accumulation. It also provides new insight into how β<sub>H</sub>-spectrin participates in ratcheting mechanisms associated with cell shape change.

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