Competition between myosin II and β-spectrin regulates cytoskeletal tension.

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