TY - JOUR
T1 - A Hip1R-cortactin complex negatively regulates actin assembly associated with endocytosis
AU - Le Clainche, Christophe
AU - Pauly, Barbara S.
AU - Zhang, Claire X.
AU - Engqvist-Goldstein, Åsa E.Y.
AU - Cunningham, Kimberley
AU - Drubin, David G.
PY - 2007/3/7
Y1 - 2007/3/7
N2 - Actin polymerization plays a critical role in clathrin-mediated endocytosis in many cell types, but how polymerization is regulated is not known. Hip1R may negatively regulate actin assembly during endocytosis because its depletion increases actin assembly at endocytic sites. Here, we show that the C-terminal proline-rich domain of Hip1R binds to the SH3 domain of cortactin, a protein that binds to dynamin, actin filaments and the Arp2/3 complex. We demonstrate that Hip1R deleted for the cortactin-binding site loses its ability to rescue fully the formation of abnormal actin structures at endocytic sites induced by Hip1R siRNA. To determine when this complex might function during endocytosis, we performed live cell imaging. The maximum in vivo recruitment of Hip1R, clathrin and cortactin to endocytic sites was coincident, and all three proteins disappeared together upon formation of a clathrin-coated vesicle. Finally, we showed that Hip1R inhibits actin assembly by forming a complex with cortactin that blocks actin filament barbed end elongation.
AB - Actin polymerization plays a critical role in clathrin-mediated endocytosis in many cell types, but how polymerization is regulated is not known. Hip1R may negatively regulate actin assembly during endocytosis because its depletion increases actin assembly at endocytic sites. Here, we show that the C-terminal proline-rich domain of Hip1R binds to the SH3 domain of cortactin, a protein that binds to dynamin, actin filaments and the Arp2/3 complex. We demonstrate that Hip1R deleted for the cortactin-binding site loses its ability to rescue fully the formation of abnormal actin structures at endocytic sites induced by Hip1R siRNA. To determine when this complex might function during endocytosis, we performed live cell imaging. The maximum in vivo recruitment of Hip1R, clathrin and cortactin to endocytic sites was coincident, and all three proteins disappeared together upon formation of a clathrin-coated vesicle. Finally, we showed that Hip1R inhibits actin assembly by forming a complex with cortactin that blocks actin filament barbed end elongation.
KW - Actin
KW - Cortactin
KW - Endocytosis
KW - Hip1R
KW - Huntingtin
UR - http://www.scopus.com/inward/record.url?scp=33947100549&partnerID=8YFLogxK
U2 - 10.1038/sj.emboj.7601576
DO - 10.1038/sj.emboj.7601576
M3 - Article
C2 - 17318189
AN - SCOPUS:33947100549
SN - 0261-4189
VL - 26
SP - 1199
EP - 1210
JO - EMBO Journal
JF - EMBO Journal
IS - 5
ER -