TY - JOUR
T1 - Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation
AU - Oser, Matthew
AU - Yamaguchi, Hideki
AU - Mader, Christopher C.
AU - Bravo-Cordero, J. J.
AU - Arias, Marianela
AU - Chen, Xiaoming
AU - DesMarais, Vera
AU - Van Rheenen, Jacco
AU - Koleske, Anthony J.
AU - Condeelis, John
PY - 2009/8/24
Y1 - 2009/8/24
N2 - Invadopodia are matrix-degrading membrane protrusions in invasive carcinoma cells. The mechanisms regulating invadopodium assembly and maturation are not understood. We have dissected the stages of invadopodium assembly and maturation and show that invadopodia use cortactin phosphorylation as a master switch during these processes. In particular, cortactin phosphorylation was found to regulate cofilin and Arp2/3 complex-dependent actin polymerization. Cortactin directly binds cofilin and inhibits its severing activity. Cortactin phosphorylation is required to release this inhibition so cofilin can sever actin filaments to create barbed ends at invadopodia to support Arp2/3-dependent actin polymerization. After barbed end formation, cortactin is dephosphorylated, which blocks cofilin severing activity thereby stabilizing invadopodia. These findings identify novel mechanisms for actin polymerization in the invadopodia of metastatic carcinoma cells and define four distinct stages of invadopodium assembly and maturation consisting of invadopodium precursor formation, actin polymerization, stabilization, and matrix degradation.
AB - Invadopodia are matrix-degrading membrane protrusions in invasive carcinoma cells. The mechanisms regulating invadopodium assembly and maturation are not understood. We have dissected the stages of invadopodium assembly and maturation and show that invadopodia use cortactin phosphorylation as a master switch during these processes. In particular, cortactin phosphorylation was found to regulate cofilin and Arp2/3 complex-dependent actin polymerization. Cortactin directly binds cofilin and inhibits its severing activity. Cortactin phosphorylation is required to release this inhibition so cofilin can sever actin filaments to create barbed ends at invadopodia to support Arp2/3-dependent actin polymerization. After barbed end formation, cortactin is dephosphorylated, which blocks cofilin severing activity thereby stabilizing invadopodia. These findings identify novel mechanisms for actin polymerization in the invadopodia of metastatic carcinoma cells and define four distinct stages of invadopodium assembly and maturation consisting of invadopodium precursor formation, actin polymerization, stabilization, and matrix degradation.
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U2 - 10.1083/jcb.200812176
DO - 10.1083/jcb.200812176
M3 - Article
C2 - 19704022
AN - SCOPUS:69449096397
SN - 0021-9525
VL - 186
SP - 571
EP - 587
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -