A role of cofilin/destrin in reorganization of actin cytoskeleton in response to stresses and cell stimuli.
1. Cofilin is an essential actin-regulating protein widely distributed in all eucaryotes. The structure and function of cofilin are conserved during evolution. 2. Cofilin depolymerizes F-actin in vitro at alkaline pH and severs F-actin in vitro at pH lower than 7.3. Overexpression of cofilin in viable cells induced bundles of actin filaments suggesting that the severing activity rather than the actin-depolymerizing or monomeric actin-sequestering activity is physiologically significant in vivo. 3. The actin bundle formation induced by overexpression of cofilin is accompanied with an increase in cell motility of Dictyostelium cells. 4. In higher vertebrates, the actin-binding activity of cofilin is negatively regulated by phosphorylation on its Ser-3 residue. The actin-binding activity is essential for yeast cells to grow. 5. Stresses and various cell stimuli activate cofilin by inducing dephosphorylation of cofilin in resting vertebrate cells. 6. Cofilin has an nuclear localization signal sequence and translocates into the nucleus together with actin in response to various stresses. Functional roles of cofilin/actin in the nucleus remain to be elucidated. 7. Tertiary structure of destrin (cofilin) resembles that of gelsolin segment 1 and well explains its functions such as Ca(2+)-independent actin binding activity.
Yahara
I
I
Department of Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
Aizawa
H
H
Moriyama
K
K
Iida
K
K
Yonezawa
N
N
Nishida
E
E
Hatanaka
H
H
Inagaki
F
F
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002477:Cells; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism; D051345:Destrin; D004023:Dictyostelium / Q000378:metabolism; D005057:Eukaryotic Cells / Q000378:metabolism; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine
D051339:Actin Depolymerizing Factors; D000199:Actins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C495824:DSTN protein, human; D051345:Destrin; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D012694:Serine