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TitleCofilactin filaments regulate filopodial structure and dynamics in neuronal growth cones.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 2439, Year 2022
Publish dateMay 4, 2022
AuthorsRyan K Hylton / Jessica E Heebner / Michael A Grillo / Matthew T Swulius /
PubMed AbstractCofilin 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- ...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.
External linksNat Commun / PubMed:35508487 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution12.5 - 20.2 Å
Structure data

EMDB-26214: F-actin from neuronal growth cone filopodium
Method: EM (subtomogram averaging) / Resolution: 20.2 Å

EMDB-26215: Cofilactin filament from neuronal growth cone filopodia
Method: EM (subtomogram averaging) / Resolution: 12.5 Å

Source
  • Rattus norvegicus (Norway rat)

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