Disease relevance of Dstn

• To directly investigate the role of cofilin activation on the actin cytoskeleton during ischemia, MS1 cells were infected with adenoviruses containing the cDNAs for wild-type Xenopus laevis ADF/cofilin green fluorescent protein [XAC(wt)-GFP], GFP, and the constitutively active and inactive isoforms XAC(S3A)-GFP and XAC(S3E)-GFP [1].
• RESULTS: In corn1/corn1 mice, focal areas of corneal epithelial hyperplasia alternate with epithelium with normal appearance [2].
• However, a significant increase of cofilin amount, but not of ADF amount, was observed in these muscles of the dystrophic animals, when the symptom of muscular dystrophy became evident [3].

High impact information on Dstn

• This review addresses aspects of ADF/cofilin structure, dynamics, regulation and function [4].
• The actin-depolymerizing factor (ADF)/cofilins are a family of essential actin regulatory proteins, ubiquitous among eukaryotes, that enhance the turnover of actin by regulating the rate constants of polymerization and depolymerization at filament ends, changing the twist of the filament and severing actin filaments [4].
• The activity of ADF/cofilin is regulated by a variety of mechanisms, including specific phosphorylation and dephosphorylation [4].
• Neurodegenerative stimuli induce persistent ADF/cofilin-actin rods that disrupt distal neurite function [5].
• Aberrant actin cytoskeleton leads to accelerated proliferation of corneal epithelial cells in mice deficient for destrin (actin depolymerizing factor) [6].

Biological context of Dstn

• Cofilin-1 and ADF seem to play overlapping roles in cells, because the knockdown phenotype of either protein could be rescued by overexpression of the other one [7].
• These data suggest that mammalian ADF and cofilin-1 promote cytoskeletal dynamics by depolymerizing actin filaments and that this activity is critical for several processes such as cytokinesis and cell motility [7].
• Depleting cofilin-1 and/or ADF by siRNA leads to an accumulation of F-actin and to an increase in cell size [7].
• Although ADF is overexpressed in mutant embryos, this cannot compensate the lack of n-cofilin, suggesting that they might have a different function in embryonic development [8].
• Our data suggest that in mammalian development, regulation of the actin cytoskeleton by the F-actin depolymerizing factor n-cofilin is critical for epithelial-mesenchymal type of cell shape changes as well as cell proliferation [8].

Anatomical context of Dstn

• Actin-depolymerizing factor (ADF)/cofilins are essential regulators of actin filament turnover [9].
• Cofilin-2 is expressed in muscle cells and ADF is restricted to epithelia and endothelia [9].
• Cofilin/ADF proteins are a ubiquitously expressed family of F-actin depolymerizing factors found in eukaryotic cells including plants [8].
• The actin depolymerizing factor n-cofilin is essential for neural tube morphogenesis and neural crest cell migration [8].
• Here we show that mediators of neurodegeneration induce the rapid formation of transient or persistent rod-like inclusions containing ADF/cofilin and actin in axons and dendrites of cultured hippocampal neurons [5].

Associations of Dstn with chemical compounds

• In higher vertebrates, cells often express as many as three different ADF/cofilin genes and each of these proteins may be phosphorylated on serine 3, giving rise to up to six different species [10].
• In cultured cells, cofilin, as well as ADF, translocates from the cytoplasm into the nucleus together with actin and forms rod-like structures in response to heat shock or dimethylsulfoxide (DMSO) treatment [11].

Other interactions of Dstn

• Spontaneous corneal hem- and lymphangiogenesis in mice with destrin-mutation depend on VEGFR3 signaling [12].
• There was no change in total actin, profilin, and cofilin/actin depolymerizing factor content [13].

Analytical, diagnostic and therapeutic context of Dstn

• Here, Western blotting was used with chemiluminescence substrates of different sensitivities to determine the relative immunoreactivities of different polyclonal rabbit antibodies and a mouse monoclonal antibody to purified ADF/cofilins from plants, protists, nematodes, insects, echinoderms, birds, and mammals [10].
• Anatomic changes were demonstrated in corn1 and control A.By/SnJ mice from day 10 of gestation of 8 months of age by routine techniques of light microscopic and scanning electron microscopy [14].
• From immunocross-reactivities and sequence alignments, the principal epitope in mammalian ADF and cofilin-1 recognized by an antibody raised against avian ADF was identified [10].
• Sequence analysis of mammalian and avian isoforms shows a consistent pattern of charge differences in regions of the protein associated with F-actin-binding that may account for the differences in activity between ADF and cofilin [15].

References