p120 catenin regulates lamellipodial dynamics and cell adhesion in cooperation with cortactin.
The armadillo-family protein, p120 catenin (p120), binds to the juxtamembrane domain of classical cadherins and increases cell-cell junction stability. Overexpression of p120 modulates the activity of Rho family GTPases and augments cell migratory ability. Here we show that down-regulation of p120 in epithelial MCF-7 cells by siRNA leads to a striking decrease in lamellipodial persistence and focal adhesion formation. Similar alterations in lamellipodial activity were observed in MCF-7 cells treated with siRNA to cortactin, an activator of Arp2/3-dependent actin polymerization. We found that, in many cell types, p120 is colocalized with cortactin-containing actin structures not only at cell-cell junctions, but also at extrajunctional sites including membrane ruffles and actin-rich halos around endocytotic vesicles. p120 depletion led to dramatic loss of cortactin and its partner, Arp3, from the cell leading edges. Cortactin and p120 are shown to directly interact with each other via the cortactin N-terminal region. We propose that the mechanism underlying p120 functions at the leading edge involves its cooperation with cortactin.
Boguslavsky
Shlomit
S
*Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Grosheva
Inna
I
Landau
Elad
E
Shtutman
Michael
M
Cohen
Miriam
M
Arnold
Katya
K
Feinstein
Elena
E
Geiger
Benjamin
B
Bershadsky
Alexander
A
D051378:Actin-Related Protein 3 / Q000378:metabolism*; D051177:Catenins; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism* / Q000502:physiology*; D045744:Cell Line, Tumor; D051356:Cortactin / Q000378:metabolism*; D004847:Epithelial Cells; D022001:Focal Adhesions; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism* / Q000502:physiology*; D011485:Protein Binding; D011554:Pseudopodia / Q000378:metabolism*; D000095002:Delta Catenin
C495928:ACTR3 protein, human; D051378:Actin-Related Protein 3; C495868:CTTN protein, human; D051177:Catenins; D015815:Cell Adhesion Molecules; D051356:Cortactin; D010750:Phosphoproteins; D000095002:Delta Catenin; C000722347:CTNND1 protein, human