Article
- The EMBO Journal (2007) 26, 1199 - 1210
- doi:10.1038/sj.emboj.7601576
Published online: 22 February 2007
Subject Categories:
A Hip1R–cortactin complex negatively regulates actin assembly associated with endocytosis
Christophe Le Clainche1,a, Barbara S Pauly1, Claire X Zhang1, Åsa E Y Engqvist-Goldstein1, Kimberley Cunningham1 and David G Drubin1
- Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA
Correspondence to:
David G Drubin, Department of Molecular and Cell Biology, University of California, 16 Barker Hall, Berkeley, CA 94720-3202, USA. Tel.: +1 510 642 3692; Fax: +1 510 643 0062; E-mail: Drubin@socrates.berkeley.edu
aPresent address: Laboratoire d'Enzymologie et Biochimie Structurales, CNRS, 91198 Gif-sur -Yvette, France
Received 20 March 2006; Accepted 4 January 2007
Abstract
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.
Keywords:
- actin,
- cortactin,
- endocytosis,
- Hip1R,
- huntingtin
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