Abi, Sra1, and Kette control the stability and localization of SCAR/WAVE to regulate the formation of actin-based protrusions

Curr Biol. 2003 Oct 28;13(21):1867-75. doi: 10.1016/j.cub.2003.10.005.


Background: In animal cells, GTPase signaling pathways are thought to generate cellular protrusions by modulating the activity of downstream actin-regulatory proteins. Although the molecular events linking activation of a GTPase to the formation of an actin-based process with a characteristic morphology are incompletely understood, Rac-GTP is thought to promote the activation of SCAR/WAVE, whereas Cdc42 is thought to initiate the formation of filopodia through WASP. SCAR and WASP then activate the Arp2/3 complex to nucleate the formation of new actin filaments, which through polymerization exert a protrusive force on the membrane.

Results: Using RNAi to screen for genes regulating cell form in an adherent Drosophila cell line, we identified a set of genes, including Abi/E3B1, that are absolutely required for the formation of dynamic protrusions. These genes delineate a pathway from Cdc42 and Rac to SCAR and the Arp2/3 complex. Efforts to place Abi in this signaling hierarchy revealed that Abi and two components of a recently identified SCAR complex, Sra1 (p140/PIR121/CYFIP) and Kette (Nap1/Hem), protect SCAR from proteasome-mediated degradation and are critical for SCAR localization and for the generation of Arp2/3-dependent protrusions.

Conclusions: In Drosophila cells, SCAR is regulated by Abi, Kette, and Sra1, components of a conserved regulatory SCAR complex. By controlling the stability, localization, and function of SCAR, these proteins may help to ensure that Arp2/3 activation and the generation of actin-based protrusions remain strictly dependant on local GTPase signaling.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Blotting, Western
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Drosophila / physiology
  • Drosophila Proteins / metabolism*
  • Fluorescent Antibody Technique
  • Microfilament Proteins / metabolism*
  • Pseudopodia / metabolism
  • Pseudopodia / physiology*
  • RNA Interference
  • Signal Transduction*
  • Wiskott-Aldrich Syndrome Protein Family


  • Abi protein, Drosophila
  • Actins
  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Drosophila Proteins
  • Microfilament Proteins
  • SCAR protein, Drosophila
  • Sra-1 protein, Drosophila
  • Wiskott-Aldrich Syndrome Protein Family
  • hem protein, Drosophila