RT Journal Article SR Electronic T1 Competition between myosin II and βH-Spectrin regulates cytoskeletal tension JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.12.01.518662 DO 10.1101/2022.12.01.518662 A1 Consuelo Ibar A1 Krishna Chinthalapudi A1 Sarah M. Heissler A1 Kenneth D. Irvine YR 2022 UL http://biorxiv.org/content/early/2022/12/01/2022.12.01.518662.abstract AB 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 StatementThe authors have declared no competing interest.