RT Journal Article SR Electronic T1 Cofilin Regulates Filopodial Structure and Flexibility in Neuronal Growth Cones JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.09.17.460569 DO 10.1101/2021.09.17.460569 A1 Ryan Hylton A1 Jessica Heebner A1 Michael Grillo A1 Matthew Swulius YR 2021 UL http://biorxiv.org/content/early/2021/09/22/2021.09.17.460569.abstract AB Cofilin is best known for its ability to sever actin filaments, and facilitate cytoskeletal recycling inside of cells. At higher concentrations, in vitro, cofilin stabilizes a more flexible, hyper-twisted state of actin known as “cofilactin”, but a structural role for cofilactin, in situ, has not been observed. Combining cryo-electron tomography and live-cell imaging in neuronal growth cones, we show that filopodial actin bundles can switch between a fascin-linked and a cofilin-decorated state, composed of hyper-twisted cofilactin filaments. These cofilactin bundles contribute to the flexibility of filopodial actin networks, thus regulating growth cone searching dynamics. Our results provide mechanistic insight into the processes underlying proper brain development, as well as fundamentals of cytoskeletal mechanics inside confined cellular spaces.Competing Interest StatementThe authors have declared no competing interest.