Mical, an enzyme mediating redox reactions, is known to promote actin remodelling in response to semaphorin signalling by disassembling actin filaments. However, the precise mechanism of Mical-dependent F-actin disassembly and the identity of Mical substrates have remained obscure. Hung et al. now report that Mical enzymatically modifies a specific actin residue to promote F-actin severing (Science 334, 1710–1713; 2011).

Using in vitro biochemical assays and microscopy techniques, the authors demonstrated that F-actin activates the enzymatic activity of Mical to promote actin filament severing and prevent repolymerization by stably and specifically modifying actin subunits at methionines 44 and 47 through the addition of oxygen. Based on previous knowledge of actin structure, these modifications were predicted to affect the interaction between F-actin subunits. The authors used point mutations to establish that residue Met 44 of actin was essential for the F-actin-severing function of Mical. Manipulation of Mical levels is known to generate abnormal bristle cell processes in Drosophila. In the present study, mutation of the Met 44 actin residue suppressed Mical overexpression phenotypes and phenocopied Mical loss-of-function effects in Drosophila. Together, these findings establish actin as a direct substrate of Mical and reveal a specific oxidation-dependent mechanism to regulate actin filament dynamics and cell processes in vivo.