The three mouse actin-depolymerizing factor/cofilins evolved to fulfill cell-type-specific requirements for actin dynamics.
Actin-depolymerizing factor (ADF)/cofilins are essential regulators of actin filament turnover. Several ADF/cofilin isoforms are found in multicellular organisms, but their biological differences have remained unclear. Herein, we show that three ADF/cofilins exist in mouse and most likely in all other mammalian species. Northern blot and in situ hybridization analyses demonstrate that cofilin-1 is expressed in most cell types of embryos and adult mice. Cofilin-2 is expressed in muscle cells and ADF is restricted to epithelia and endothelia. Although the three mouse ADF/cofilins do not show actin isoform specificity, they all depolymerize platelet actin filaments more efficiently than muscle actin. Furthermore, these ADF/cofilins are biochemically different. The epithelial-specific ADF is the most efficient in turning over actin filaments and promotes a stronger pH-dependent actin filament disassembly than the two other isoforms. The muscle-specific cofilin-2 has a weaker actin filament depolymerization activity and displays a 5-10-fold higher affinity for ATP-actin monomers than cofilin-1 and ADF. In steady-state assays, cofilin-2 also promotes filament assembly rather than disassembly. Taken together, these data suggest that the three biochemically distinct mammalian ADF/cofilin isoforms evolved to fulfill specific requirements for actin filament dynamics in different cell types.
Vartiainen
Maria K
MK
Programs in Cellular Biotechnology, Institute of Biotechnology, Viikki Biocenter, University of Helsinki, Helsinki, 00014 Finland.
Mustonen
Tuija
T
Mattila
Pieta K
PK
Ojala
Pauli J
PJ
Thesleff
Irma
I
Partanen
Juha
J
Lappalainen
Pekka
P
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D051338:Cofilin 1; D051340:Cofilin 2; D051345:Destrin; D004727:Endothelium / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D019143:Evolution, Molecular; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D010802:Phylogeny; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D014018:Tissue Distribution
D051339:Actin Depolymerizing Factors; D000199:Actins; C495815:CFL2 protein, human; C495811:Cfl1 protein, mouse; C495816:Cfl2 protein, mouse; D051338:Cofilin 1; D051340:Cofilin 2; C495824:DSTN protein, human; D051345:Destrin; C495825:Dstn protein, mouse; D008840:Microfilament Proteins; D020033:Protein Isoforms