Abi1 regulates the activity of N-WASP and WAVE in distinct actin-based processes.
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.
Innocenti
Metello
M
IFOM, Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20134, Milan, Italy.
Gerboth
Silke
S
Rottner
Klemens
K
Lai
Frank P L
FP
Hertzog
Maud
M
Stradal
Theresia E B
TE
Frittoli
Emanuela
E
Didry
Dominique
D
Polo
Simona
S
Disanza
Andrea
A
Benesch
Stefanie
S
Di Fiore
Pier Paolo
PP
Carlier
Marie-France
MF
Scita
Giorgio
G
D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003598:Cytoskeletal Proteins; D066246:ErbB Receptors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D011990:Receptors, Transferrin / Q000378:metabolism; D022161:Transport Vesicles / Q000378:metabolism; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000235:genetics / Q000378:metabolism*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism* / Q000502:physiology; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
C513733:ABI1 protein, human; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D011990:Receptors, Transferrin; C114864:WASF1 protein, human; C495771:WASL protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D066246:ErbB Receptors; D020764:cdc42 GTP-Binding Protein