A step-by-step guide to fragmenting bundled actin filaments

Abstract

There has long been conflicting evidence as to how bundled actin filaments, found in cellular structures such as filopodia, are disassembled. In this issue, Chikireddy et al. (https://doi.org/10.1083/jcb.202312106) provide a detailed in vitro analysis of the steps involved in fragmentation of fascin-bundled actin filaments and propose a novel mechanism for severing two-filament bundles.

Figure 1.

Mechanisms for single filament and two-filament bundle fragmentation by cofilin. (A) On a single actin filament (A), cofilin binds, spreads, and severs filaments. (B and C) In fascin-bundled actin filaments (C), as commonly found in filopodia (B), the initial binding and spreading of cofilin is inhibited. Once fascin dissociates, cofilin can bind along one filament and through “interfilament cooperativity” promotes cofilin binding to the adjacent filament at a faster rate than the initial binding event or on individual filaments. Severing of the first filament, then the second filament in the bundle results in bundle fragmentation.