Abi1 regulates the activity of N-WASP and WAVE in distinct actin-based processes

Metello Innocenti, Silke Gerboth, Klemens Rottner, Frank P L Lai, Maud Hertzog, Theresia E B Stradal, Emanuela Frittoli, Dominique Didry, Simona Polo, Andrea Disanza, Stefanie Benesch, Pier Paolo Di Fiore, Marie France Carlier, Giorgio Scita

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)969-976
Number of pages8
JournalNature Cell Biology
Volume7
Issue number10
DOIs
Publication statusPublished - Oct 2005

ASJC Scopus subject areas

  • Cell Biology

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