Abstract
Background: Previous work has led to the hypothesis that cofilin severing, as regulated by PLC, is involved in chemotactic sensing. We have tested this hypothesis by investigating whether activation of endogenous cofilin is spatially and temporally linked to sensing an EGF point source in carcinoma cells. Results: We demonstrate that inhibition of endogenous cofilin activity with either siRNA or overexpression of LIMK suppresses directional sensing in carcinoma cells. LIMK siRNA knockdown, which suppresses cofilin phosphorylation, and microinjection of S3C cofilin, a cofilin mutant that is constitutively active and not phosphorylated by LIMK, also inhibits directional sensing and chemotaxis. These results indicate that phosphorylation of cofilin by LIMK, in addition to cofilin activity, is required for chemotaxis. Cofilin activity concentrates rapidly at the newly formed leading edge facing the gradient, whereas cofilin phosphorylation increases throughout the cell. Quantification of these results indicates that the amplification of asymmetric actin polymerization required for protrusion toward the EGF gradient occurs at the level of cofilin but not at the level of PLC activation by EGFR. Conclusions: These results indicate that local activation of cofilin by PLC and its global inactivation by LIMK phosphorylation combine to generate the local asymmetry of actin polymerization required for chemotaxis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2193-2205 |
| Number of pages | 13 |
| Journal | Current Biology |
| Volume | 16 |
| Issue number | 22 |
| DOIs | |
| State | Published - Nov 21 2006 |
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Keywords
- CELLBIO
ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
Cite this
Spatial and Temporal Control of Cofilin Activity Is Required for Directional Sensing during Chemotaxis. / Mouneimne, Ghassan; Desmarais, Vera M.; Sidani, Mazen; Scemes, Eliana; Wang, Weigang; Song, Xiaoyan; Eddy, Robert J.; Condeelis, John S.
In: Current Biology, Vol. 16, No. 22, 21.11.2006, p. 2193-2205.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Spatial and Temporal Control of Cofilin Activity Is Required for Directional Sensing during Chemotaxis
AU - Mouneimne, Ghassan
AU - Desmarais, Vera M.
AU - Sidani, Mazen
AU - Scemes, Eliana
AU - Wang, Weigang
AU - Song, Xiaoyan
AU - Eddy, Robert J.
AU - Condeelis, John S.
PY - 2006/11/21
Y1 - 2006/11/21
N2 - Background: Previous work has led to the hypothesis that cofilin severing, as regulated by PLC, is involved in chemotactic sensing. We have tested this hypothesis by investigating whether activation of endogenous cofilin is spatially and temporally linked to sensing an EGF point source in carcinoma cells. Results: We demonstrate that inhibition of endogenous cofilin activity with either siRNA or overexpression of LIMK suppresses directional sensing in carcinoma cells. LIMK siRNA knockdown, which suppresses cofilin phosphorylation, and microinjection of S3C cofilin, a cofilin mutant that is constitutively active and not phosphorylated by LIMK, also inhibits directional sensing and chemotaxis. These results indicate that phosphorylation of cofilin by LIMK, in addition to cofilin activity, is required for chemotaxis. Cofilin activity concentrates rapidly at the newly formed leading edge facing the gradient, whereas cofilin phosphorylation increases throughout the cell. Quantification of these results indicates that the amplification of asymmetric actin polymerization required for protrusion toward the EGF gradient occurs at the level of cofilin but not at the level of PLC activation by EGFR. Conclusions: These results indicate that local activation of cofilin by PLC and its global inactivation by LIMK phosphorylation combine to generate the local asymmetry of actin polymerization required for chemotaxis.
AB - Background: Previous work has led to the hypothesis that cofilin severing, as regulated by PLC, is involved in chemotactic sensing. We have tested this hypothesis by investigating whether activation of endogenous cofilin is spatially and temporally linked to sensing an EGF point source in carcinoma cells. Results: We demonstrate that inhibition of endogenous cofilin activity with either siRNA or overexpression of LIMK suppresses directional sensing in carcinoma cells. LIMK siRNA knockdown, which suppresses cofilin phosphorylation, and microinjection of S3C cofilin, a cofilin mutant that is constitutively active and not phosphorylated by LIMK, also inhibits directional sensing and chemotaxis. These results indicate that phosphorylation of cofilin by LIMK, in addition to cofilin activity, is required for chemotaxis. Cofilin activity concentrates rapidly at the newly formed leading edge facing the gradient, whereas cofilin phosphorylation increases throughout the cell. Quantification of these results indicates that the amplification of asymmetric actin polymerization required for protrusion toward the EGF gradient occurs at the level of cofilin but not at the level of PLC activation by EGFR. Conclusions: These results indicate that local activation of cofilin by PLC and its global inactivation by LIMK phosphorylation combine to generate the local asymmetry of actin polymerization required for chemotaxis.
KW - CELLBIO
UR - http://www.scopus.com/inward/record.url?scp=33750948427&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750948427&partnerID=8YFLogxK
U2 - 10.1016/j.cub.2006.09.016
DO - 10.1016/j.cub.2006.09.016
M3 - Article
C2 - 17113383
AN - SCOPUS:33750948427
VL - 16
SP - 2193
EP - 2205
JO - Current Biology
JF - Current Biology
SN - 0960-9822
IS - 22
ER -