Letter abstract
Nature Cell Biology 7, 969 - 976 (2005)
Published online: 11 September 2005 | doi:10.1038/ncb1304
Abi1 regulates the activity of N-WASP and WAVE in distinct actin-based processes
Metello Innocenti1,2, Silke Gerboth1,2, Klemens Rottner3, Frank P. L. Lai3, Maud Hertzog1,2,5, Theresia E. B. Stradal4, Emanuela Frittoli1,2, Dominique Didry5, Simona Polo1,2, Andrea Disanza1,2, Stefanie Benesch3, Pier Paolo Di Fiore1,2,6, Marie-France Carlier5 & Giorgio Scita1,2
Neural Wiskott–Aldrich syndrome protein (N-WASP) and WAVE are members of a family of proteins that use the Arp2/3 complex to stimulate actin assembly in actin-based motile processes. By entering into distinct macromolecular complexes, they act as convergent nodes of different signalling pathways. The role of WAVE in generating lamellipodial protrusion during cell migration is well established. Conversely, the precise cellular functions of N-WASP have remained elusive. Here, we report that Abi1, an essential component of the WAVE protein complex, also has a critical role in regulating N-WASP-dependent function. Consistently, Abi1 binds to N-WASP with nanomolar affinity and, cooperating with Cdc42, potently induces N-WASP activity in vitro. Molecular genetic approaches demonstrate that Abi1 and WAVE, but not N-WASP, are essential for Rac-dependent membrane protrusion and macropinocytosis. Conversely, Abi1 and N-WASP, but not WAVE, regulate actin-based vesicular transport, epidermal growth factor receptor (EGFR) endocytosis, and EGFR and transferrin receptor (TfR) cell-surface distribution. Thus, Abi1 is a dual regulator of WAVE and N-WASP activities in specific processes that are dependent on actin dynamics.
- IFOM, Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20134, Milan, Italy.
- Department of Experimental Oncology, Istituto Europeo di Oncologia (IEO), Via Ripamonti 435, 20141, Milan, Italy.
- Cytoskeleton Dynamics Group, German Research Centre for Biotechnology (GBF), Mascheroder Weg 1, D-38124 Braunschweig, Germany.
- Signalling and Motility Group, German Research Centre for Biotechnology (GBF), Mascheroder Weg 1, D-38124 Braunschweig, Germany.
- Dynamique du Cytosquelette Laboratoire d'Enzymologie et Biochimie Structurales, C.N.R.S. 91198 Gif-sur-Yvette, France.
- Dipartimento di Medicina, Chirurgia ed Odontoiatria, Universita' degli Studi di Milano, 20122 Milan, Italy.
Correspondence to: Giorgio Scita1,2 e-mail: giorgio.scita@ifom-ieo-campus.it
Correspondence to: Marie-France Carlier5 e-mail: carlier@lebs.cnrs-gif.fr
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