title: Cofilin nuclear-cytoplasmic shuttling affects cofilin-actin rod formation during stress.
abstract: Cofilin protein is involved in regulating the actin cytoskeleton during typical steady state conditions, as well as during cell stress conditions where cofilin saturates F-actin, forming cofilin-actin rods. Cofilin can enter the nucleus through an active nuclear localization signal (NLS), accumulating in nuclear actin rods during stress. Here, we characterize the active nuclear export of cofilin through a leptomycin-B-sensitive, CRM1-dependent, nuclear export signal (NES). We also redefine the NLS of cofilin as a bipartite NLS, with an additional basic epitope required for nuclear localization. Using fluorescence lifetime imaging microscopy (FLIM) and Förster resonant energy transfer (FRET) between cofilin moieties and actin, as well as automated image analysis in live cells, we have defined subtle mutations in the cofilin NLS that allow cofilin to bind actin in vivo and affect cofilin dynamics during stress. We further define the requirement of cofilin-actin rod formation in a system of cell stress by temporal live-cell imaging. We propose that cofilin nuclear shuttling is critical for the cofilin-actin rod stress response with cofilin dynamically communicating between the nucleus and cytoplasm during cell stress.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street West, Hamilton, Ontario,  Canada, L8N 3Z5.
authors.forename: Lise Nicole
authors.initials: LN
authors.lastname: Munsie
authors.forename: Carly R
authors.initials: CR
authors.lastname: Desmond
authors.forename: Ray
authors.initials: R
authors.lastname: Truant
mesh_terms: D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D051338:Cofilin 1 / Q000737:chemistry / Q000378:metabolism*; D017124:Conserved Sequence; D055785:Gene Knockdown Techniques; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation; D049790:Nuclear Export Signals; D019913:Nuclear Localization Signals / Q000737:chemistry / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013312:Stress, Physiological; D000097606:Exportin 1 Protein
chemical_list: D000199:Actins; D051338:Cofilin 1; D028884:Karyopherins; D050505:Mutant Proteins; D049790:Nuclear Export Signals; D019913:Nuclear Localization Signals; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein