Title |
N-WASP regulates the epithelial junctional actin cytoskeleton through a non-canonical post-nucleation pathway
|
---|---|
Published in |
Nature Cell Biology, July 2011
|
DOI | 10.1038/ncb2290 |
Pubmed ID | |
Authors |
Eva M. Kovacs, Suzie Verma, Radiya G. Ali, Aparna Ratheesh, Nicholas A. Hamilton, Anna Akhmanova, Alpha S. Yap |
Abstract |
N-WASP is a major cytoskeletal regulator that stimulates Arp2/3-mediated actin nucleation. Here, we identify a nucleation-independent pathway by which N-WASP regulates the cytoskeleton and junctional integrity at the epithelial zonula adherens. N-WASP is a junctional protein whose depletion decreased junctional F-actin content and organization. However, N-WASP (also known as WASL) RNAi did not affect junctional actin nucleation, dominantly mediated by Arp2/3. Furthermore, the junctional effect of N-WASP RNAi was rescued by an N-WASP mutant that cannot directly activate Arp2/3. Instead, N-WASP stabilized newly formed actin filaments and facilitated their incorporation into apical rings at the zonula adherens. A major physiological effect of N-WASP at the zonula adherens thus occurs through a non-canonical pathway that is distinct from its capacity to activate Arp2/3. Indeed, the junctional impact of N-WASP was mediated by the WIP-family protein, WIRE, which binds to the N-WASP WH1 domain. We conclude that N-WASP-WIRE serves as an integrator that couples actin nucleation with the subsequent steps of filament stabilization and organization necessary for zonula adherens integrity. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
France | 3 | 2% |
United States | 3 | 2% |
United Kingdom | 2 | 2% |
Portugal | 1 | <1% |
Australia | 1 | <1% |
Japan | 1 | <1% |
Singapore | 1 | <1% |
Unknown | 120 | 91% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 38 | 29% |
Student > Ph. D. Student | 34 | 26% |
Professor > Associate Professor | 12 | 9% |
Student > Bachelor | 12 | 9% |
Student > Master | 9 | 7% |
Other | 18 | 14% |
Unknown | 9 | 7% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 66 | 50% |
Biochemistry, Genetics and Molecular Biology | 36 | 27% |
Medicine and Dentistry | 5 | 4% |
Neuroscience | 4 | 3% |
Physics and Astronomy | 3 | 2% |
Other | 8 | 6% |
Unknown | 10 | 8% |