Angew Chem Int Ed Engl 2014[Oct]; 53 (41): 10904-7 PMID25156888show ga
Genetically encoded, light activatable proteins furnish the means to probe biochemical pathways at specific sub-cellular locations with exquisite temporal control. However, engineering these systems to provide a dramatic jump in localized activity while retaining a low dark-state background remains a significant challenge. We describe herein an actin-remodelling protein cofilin that, when placed within the framework of a genetically encodable, light activatable heterodimerizer system, induces dramatic changes in the F-actin network and consequent cell motility upon illumination. We demonstrate that the use of a partially impaired mutant of cofilin is critical for maintaining low background activity in the dark. We also show that light-directed recruitment of the reduced activity cofilin mutants to the cytoskeleton is sufficient to induce F-actin remodeling, formation of filopodia, and directed cell motility.