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Unbalancing the phosphatidylinositol-4,5-bisphosphate-cofilin interaction impairs cell steering

(2009) MOLECULAR BIOLOGY OF THE CELL. 20(21). p.4509-4523
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Abstract
Cofilin is a key player in actin dynamics during cell migration. Its activity is regulated by ( de) phosphorylation, pH, and binding to phosphatidylinositol-4,5-bisphosphate [PI(4,5)P(2)]. Here, we here use a human cofilin-1 (D122K) mutant with increased binding affinity for PI(4,5)P(2) and slower release from the plasma membrane to study the role of the PI(4,5)P(2)-cofilin interaction in migrating cells. In fibroblasts in a background of endogenous cofilin, D122K cofilin expression negatively affects cell turning frequency. In carcinoma cells with down-regulated endogenous cofilin, D122K cofilin neither rescues the drastic morphological defects nor restores the effects in cell turning capacity, unlike what has been reported for wild-type cofilin. In cofilin knockdown cells, D122K cofilin expression promotes outgrowth of an existing lamellipod in response to epidermal growth factor (EGF) but does not result in initiation of new lamellipodia. This indicates that, next to phospho- and pH regulation, the normal release kinetics of cofilin from PI(4,5)P(2) is crucial as a local activation switch for lamellipodia initiation and as a signal for migrating cells to change direction in response to external stimuli. Our results demonstrate that the PI(4,5)P(2) regulatory mechanism, that is governed by EGF-dependent phospholipase C activation, is a determinant for the spatial and temporal control of cofilin activation required for lamellipodia initiation.
Keywords
ACTIVATES COFILIN, PHOSPHOLIPASE-C, PHOSPHOINOSITIDE-BINDING, MAMMARY-TUMORS, ARP2/3 COMPLEX, CARCINOMA-CELLS, ACTIN-DEPOLYMERIZING FACTOR, FILAMENT TURNOVER, BINDING-PROTEIN, COFILIN ACTIVITY

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Citation

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MLA
Leyman, Shirley et al. “Unbalancing the Phosphatidylinositol-4,5-bisphosphate-cofilin Interaction Impairs Cell Steering.” MOLECULAR BIOLOGY OF THE CELL 20.21 (2009): 4509–4523. Print.
APA
Leyman, S., Sidani, M., Ritsma, L., WATERSCHOOT, D., Eddy, R., Dewitte, D., Debeir, O., et al. (2009). Unbalancing the phosphatidylinositol-4,5-bisphosphate-cofilin interaction impairs cell steering. MOLECULAR BIOLOGY OF THE CELL, 20(21), 4509–4523.
Chicago author-date
Leyman, Shirley, Mazen Sidani, Laila Ritsma, DAVY WATERSCHOOT, Robert Eddy, Daisy Dewitte, Olivier Debeir, et al. 2009. “Unbalancing the Phosphatidylinositol-4,5-bisphosphate-cofilin Interaction Impairs Cell Steering.” Molecular Biology of the Cell 20 (21): 4509–4523.
Chicago author-date (all authors)
Leyman, Shirley, Mazen Sidani, Laila Ritsma, DAVY WATERSCHOOT, Robert Eddy, Daisy Dewitte, Olivier Debeir, Christine Decaestecker, Joël Vandekerckhove, Jacco van Rheenen, Christophe Ampe, John Condeelis, and Marleen Van Troys. 2009. “Unbalancing the Phosphatidylinositol-4,5-bisphosphate-cofilin Interaction Impairs Cell Steering.” Molecular Biology of the Cell 20 (21): 4509–4523.
Vancouver
1.
Leyman S, Sidani M, Ritsma L, WATERSCHOOT D, Eddy R, Dewitte D, et al. Unbalancing the phosphatidylinositol-4,5-bisphosphate-cofilin interaction impairs cell steering. MOLECULAR BIOLOGY OF THE CELL. 2009;20(21):4509–23.
IEEE
[1]
S. Leyman et al., “Unbalancing the phosphatidylinositol-4,5-bisphosphate-cofilin interaction impairs cell steering,” MOLECULAR BIOLOGY OF THE CELL, vol. 20, no. 21, pp. 4509–4523, 2009.
@article{778394,
  abstract     = {Cofilin is a key player in actin dynamics during cell migration. Its activity is regulated by ( de) phosphorylation, pH, and binding to phosphatidylinositol-4,5-bisphosphate [PI(4,5)P(2)]. Here, we here use a human cofilin-1 (D122K) mutant with increased binding affinity for PI(4,5)P(2) and slower release from the plasma membrane to study the role of the PI(4,5)P(2)-cofilin interaction in migrating cells. In fibroblasts in a background of endogenous cofilin, D122K cofilin expression negatively affects cell turning frequency. In carcinoma cells with down-regulated endogenous cofilin, D122K cofilin neither rescues the drastic morphological defects nor restores the effects in cell turning capacity, unlike what has been reported for wild-type cofilin. In cofilin knockdown cells, D122K cofilin expression promotes outgrowth of an existing lamellipod in response to epidermal growth factor (EGF) but does not result in initiation of new lamellipodia. This indicates that, next to phospho- and pH regulation, the normal release kinetics of cofilin from PI(4,5)P(2) is crucial as a local activation switch for lamellipodia initiation and as a signal for migrating cells to change direction in response to external stimuli. Our results demonstrate that the PI(4,5)P(2) regulatory mechanism, that is governed by EGF-dependent phospholipase C activation, is a determinant for the spatial and temporal control of cofilin activation required for lamellipodia initiation.},
  author       = {Leyman, Shirley and Sidani, Mazen and Ritsma, Laila and WATERSCHOOT, DAVY and Eddy, Robert and Dewitte, Daisy and Debeir, Olivier and Decaestecker, Christine and Vandekerckhove, Joël and van Rheenen, Jacco and Ampe, Christophe and Condeelis, John and Van Troys, Marleen},
  issn         = {1059-1524},
  journal      = {MOLECULAR BIOLOGY OF THE CELL},
  keywords     = {ACTIVATES COFILIN,PHOSPHOLIPASE-C,PHOSPHOINOSITIDE-BINDING,MAMMARY-TUMORS,ARP2/3 COMPLEX,CARCINOMA-CELLS,ACTIN-DEPOLYMERIZING FACTOR,FILAMENT TURNOVER,BINDING-PROTEIN,COFILIN ACTIVITY},
  language     = {eng},
  number       = {21},
  pages        = {4509--4523},
  title        = {Unbalancing the phosphatidylinositol-4,5-bisphosphate-cofilin interaction impairs cell steering},
  url          = {http://dx.doi.org/10.1091/mbc.E09-02-0121},
  volume       = {20},
  year         = {2009},
}

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