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.
|Titolo:||Abi1 regulates the activity of N-WASP and WAVE in distinct actin-based processes|
SCITA, GIORGIO (Ultimo)
|Parole Chiave:||article ; binding affinity ; cell membrane ; cell surface ; cell transport ; cell vacuole ; cellular distribution ; complex formation ; controlled study ; endocytosis ; human cell ; human ; in vitro study ; megalocytosis ; molecular dynamics ; molecular genetics ; pinocytosis ; priority journal ; protein binding ; protein function ; regulatory mechanism ; Rac protein ; Wiskott Aldrich syndrome protein ; actin ; cell protein ; epidermal growth factor receptor ; protein Abi1 ; protein Cdc42 ; protein WAVE ; transferrin receptor ; unclassified drug|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||2005|
|Digital Object Identifier (DOI):||10.1038/ncb1304|
|Appare nelle tipologie:||01 - Articolo su periodico|