Cofilactin filaments regulate filopodial structure and dynamics in neuronal growth cones

Ryan K. Hylton, Jessica E. Heebner, Michael A. Grillo, Matthew T. Swulius

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Cofilin is best known for its ability to sever actin filaments and facilitate cytoskeletal recycling inside of cells, but at higher concentrations in vitro, cofilin stabilizes a more flexible, hyper-twisted state of actin known as “cofilactin”. While this filament state is well studied, a structural role for cofilactin in dynamic cellular processes has not been observed. With a combination of cryo-electron tomography and fluorescence imaging in neuronal growth cones, we observe that filopodial actin filaments switch between a fascin-linked and a cofilin-decorated state, and that cofilactin is associated with a variety of dynamic events within filopodia. The switch to cofilactin filaments occurs in a graded fashion and correlates with a decline in fascin cross-linking within the filopodia, which is associated with curvature in the bundle. Our tomographic data reveal that the hyper-twisting of actin from cofilin binding leads to a rearrangement of filament packing, which largely excludes fascin from the base of filopodia. Our results provide mechanistic insight into the fundamentals of cytoskeletal remodeling inside of confined cellular spaces, and how the interplay between fascin and cofilin regulates the dynamics of searching filopodia.

Original languageEnglish (US)
Article number2439
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General
  • General Physics and Astronomy

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