Coordination of the filament stabilizing versus destabilizing activities of cofilin through its secondary binding site on actin

Aggeli, Dimitra; Kish-Trier, Erik; Lin, Meng Chi; Haarer, Brian K.; Cingolani, Gino; Cooper, John A.; Wilkens, Stephan; Amberg, David C.

doi:10.1002/cm.21178

Cited by 14 publications

(21 citation statements)

References 86 publications

(190 reference statements)

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“…Recent biochemical, structural, and cell biological evidence has suggested that Aip1 may enhance severing by competing with Cof1 for its second binding site on F-actin, leading to filament destabilization. Indeed, in support of this model, mutants in cof1 that disrupt its second F-actin binding site were found to be hyperactive for filament severing ( Aggeli et al 2014 ).…”

Section: Mechanisms Of Actin Assembly and Turnovermentioning

confidence: 87%

Actin and Endocytosis in Budding Yeast

2015

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Endocytosis, the process whereby the plasma membrane invaginates to form vesicles, is essential for bringing many substances into the cell and for membrane turnover. The mechanism driving clathrin-mediated endocytosis (CME) involves > 50 different protein components assembling at a single location on the plasma membrane in a temporally ordered and hierarchal pathway. These proteins perform precisely choreographed steps that promote receptor recognition and clustering, membrane remodeling, and force-generating actin-filament assembly and turnover to drive membrane invagination and vesicle scission. Many critical aspects of the CME mechanism are conserved from yeast to mammals and were first elucidated in yeast, demonstrating that it is a powerful system for studying endocytosis. In this review, we describe our current mechanistic understanding of each step in the process of yeast CME, and the essential roles played by actin polymerization at these sites, while providing a historical perspective of how the landscape has changed since the preceding version of the YeastBook was published 17 years ago (1997). Finally, we discuss the key unresolved issues and where future studies might be headed.

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Section: Mechanisms Of Actin Assembly and Turnovermentioning

confidence: 87%

Actin and Endocytosis in Budding Yeast

2015

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“…In addition, it is yet to be determined precisely how AIP1 binding to a Cofilin-decorated region of a filament triggers severing. This may involve AIP1 displacing one or more Cof1 molecules from a patch to generate a local discontinuity that destabilizes filaments 44 , or AIP1 displacing one of Cofilin's two binding interactions with F-actin 45 . Finally, it will be important to study if and how Cofilin, Coronin and AIP1 work alongside other actin disassembly factors, for example, Srv2/CAP, GMF and possibly Twinfilin 16 18 46 47 .…”

Section: Discussionmentioning

confidence: 99%

Single-molecule imaging of a three-component ordered actin disassembly mechanism

et al. 2015

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Summary The mechanisms by which cells destabilize and rapidly disassemble filamentous actin networks have remained elusive; however, Coronin, Cofilin, and AIP1 have been implicated in this process. Here, using multi-wavelength single molecule fluorescence imaging, we show that mammalian Cor1B, Cof1, and AIP1 work in concert through a temporally ordered pathway to induce highly efficient severing and disassembly of actin filaments. Cor1B binds to filaments first, and dramatically accelerates the subsequent binding of Cof1, leading to heavily decorated, stabilized filaments. Cof1 in turn recruits AIP1, which rapidly triggers severing and remains bound to the newly-generated barbed ends. New growth at barbed ends generated by severing was blocked specifically in the presence of all three proteins. This activity enabled us to reconstitute and directly visualize single actin filaments being rapidly polymerized by formins at their barbed ends while simultanteously being stochastically severed and capped along their lengths, and disassembled from their pointed ends.

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“…It is also interesting to consider how sequence differences between Cof1, Cof2, and ADF account for the differences in their severing activities. Previous studies found that differences in the actin-binding residues of the three ADF/Cofilins map to the F-site [9], and a recent study on yeast Cof1 demonstrated that point mutations in its F-site drastically enhance severing activity [50]. …”

Section: Discussionmentioning

confidence: 99%

TIRF microscopy analysis of human Cof1, Cof2, and ADF effects on actin filament severing and turnover

Chin

Jansen

Goode

2016

Journal of Molecular Biology

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Dynamic remodeling and turnover of cellular actin networks requires actin filament severing by Actin-Depolymerizing Factor (ADF)/Cofilin proteins. Mammals express three different ADF/Cofilins (Cof1, Cof2, and ADF), and genetic studies suggest that in vivo they perform both overlapping and unique functions. To gain mechanistic insights into their different roles, we directly compared their G-actin and F-actin binding affinities, and quantified the actin filament severing activities of human Cof1, Cof2, and ADF using in vitro TIRF microscopy. All three ADF/Cofilins had similar affinities for G-actin and F-actin. However, Cof2 and ADF severed filaments much more efficiently than Cof1 at both lower and higher concentrations and using either muscle or platelet actin. Further, Cof2 and ADF were more effective than Cof1 in promoting ‘enhanced disassembly’ when combined with actin disassembly co-factors Coronin-1B and Actin-Interacting Protein 1 (AIP1), and these differences were observed on both preformed and actively growing filaments. To probe the mechanism underlying these differences, we used multi-wavelength TIRF microscopy to directly observe Cy3-Cof1 and Cy3-Cof2 interacting with actin filaments in real time during severing. Cof1 and Cof2 each bound to filaments with similar kinetics, yet Cof2 induced severing much more rapidly than Cof1, decreasing the time interval between initial binding on a filament and severing at the same location. These differences in ADF/Cofilin activities and mechanisms may be used in cells to tune filament turnover rates, which can vary widely for different actin structures.

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Coordination of the filament stabilizing versus destabilizing activities of cofilin through its secondary binding site on actin

Cited by 14 publications

References 86 publications

Actin and Endocytosis in Budding Yeast

Actin and Endocytosis in Budding Yeast

Single-molecule imaging of a three-component ordered actin disassembly mechanism

TIRF microscopy analysis of human Cof1, Cof2, and ADF effects on actin filament severing and turnover

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