Catastrophic actin filament bursting by cofilin, Aip1, and coronin

Abstract

Cofilin is an actin filament severing protein necessary for fast actin turnover dynamics. Coronin and Aip1 promote cofilin mediated actin filament disassembly, but the mechanism is somewhat controversial. An early model proposed that the combination of cofilin, coronin, and Aip1 disassembled filaments in bursts. A subsequent study only reported severing. Here, we used electron microscopy to show that actin filaments convert directly into globular material. A monomer trap assay also shows that the combination of all three factors produces actin monomers faster than any two factors alone. We show that coronin accelerates the release of inorganic phosphate from actin filaments and promotes highly cooperative cofilin binding to actin to create long stretches of polymer with a hypertwisted morphology. Aip1 attacks these hypertwisted regions along their sides, disintegrating them into monomers or short oligomers. The results are consistent with a catastrophic mode of disassembly, not enhanced severing alone.

Actin at stereocilia tips is regulated by mechanotransduction and ADF/cofilin

“…To decrease width, severing could rapidly destabilize actin filaments, which has been observed in cellular and biochemical contexts when CFL1 is combined with coronin, and AIP1. 48,49 Coronin localizes to stereocilia and stereocilia morphology is not maintained in AIP1 mutants, 15,50 suggesting this is a plausible mechanism. Concurrently, severing may regulate barbed end availability by removing filament ends that are bound by capping proteins such as CAPZ, TWF2, and EPS8.…”

Multiple roles for actin in secretory and endocytic pathways

“…Interestingly, ERendosome interactions promote a reduction in endosomal PI4P, which contributes to WASH activation 94 . The combination of the enrichment of coronin, generally considered an antagonist of Arp2/3 complex 95,96 , and the reduction in WASH activation might therefore terminate actin polymerization prior to scission.…”

“…The link between coronin7 and actin assembly is unclear, however. Coronins are generally considered to contribute more to actin depolymerization through effects both on Arp2/3 complex and cofilin 95,96 , though the biochemical properties of coronin7 on actin have not been studied in detail.…”

The dynamic instability of actin filament barbed ends

“…Despite insights from techniques such as single-molecule speckle microscopy, it is still unclear from which end actin filaments depolymerize, even in networks that appear to globally treadmill, such as the lamellipodium. Pointed end depolymerization alone cannot account for what is observed in cells (Miyoshi et al, 2006) and alternative mechanisms have been proposed, including brutal filament-to-monomer transitions occurring in bursts, driven by cofilin, coronin, and Aip1 (Brieher, 2013;Tang et al, 2020).…”