Srv2/cyclase-associated protein forms hexameric shurikens that directly catalyze actin filament severing by cofilin.

Faisal Chaudhry, Dennis Breitsprecher, Kristin Little, Grigory Sharov, Olga Sokolova, Bruce L Goode

Molecular biology of the cell 2013 Jan

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Actin filament severing is critical for the dynamic turnover of cellular actin networks. Cofilin severs filaments, but additional factors may be required to increase severing efficiency in vivo. Srv2/cyclase-associated protein (CAP) is a widely expressed protein with a role in binding and recycling actin monomers ascribed to domains in its C-terminus (C-Srv2). In this paper, we report a new biochemical and cellular function for Srv2/CAP in directly catalyzing cofilin-mediated severing of filaments. This function is mediated by its N-terminal half (N-Srv2), and is physically and genetically separable from C-Srv2 activities. Using dual-color total internal reflection fluorescence microscopy, we determined that N-Srv2 stimulates filament disassembly by increasing the frequency of cofilin-mediated severing without affecting cofilin binding to filaments. Structural analysis shows that N-Srv2 forms novel hexameric star-shaped structures, and disrupting oligomerization impairs N-Srv2 activities and in vivo function. Further, genetic analysis shows that the combined activities of N-Srv2 and Aip1 are essential in vivo. These observations define a novel mechanism by which the combined activities of cofilin and Srv2/CAP lead to enhanced filament severing and support an emerging view that actin disassembly is controlled not by cofilin alone, but by a more complex set of factors working in concert.

Citation

Faisal Chaudhry, Dennis Breitsprecher, Kristin Little, Grigory Sharov, Olga Sokolova, Bruce L Goode. Srv2/cyclase-associated protein forms hexameric shurikens that directly catalyze actin filament severing by cofilin. Molecular biology of the cell. 2013 Jan;24(1):31-41