Abl interactor 1 (Abi-1) wave-binding and SNARE domains regulate its nucleocytoplasmic shuttling, lamellipodium localization, and wave-1 levels

Mol Cell Biol. 2004 Jun;24(11):4979-93. doi: 10.1128/MCB.24.11.4979-4993.2004.

Abstract

The Abl interactor 1 (Abi-1) protein has been implicated in the regulation of actin dynamics and localizes to the tips of lamellipodia and filopodia. Here, we show that Abi-1 binds the actin nucleator protein Wave-1 through an amino-terminal Wave-binding (WAB) domain and that disruption of the Abi-1-Wave-1 interaction prevents Abi-1 from reaching the tip of the lamellipodium. Abi-1 binds to the Wave homology domain of Wave-1, a region that is required for translocation of Wave-1 to the lamellipodium. Mouse embryo fibroblasts that lack one allele of Abi-1 and are homozygous null for the related Abi-2 protein exhibit decreased Wave-1 protein levels. This phenotype is rescued by Abi-1 proteins that retain Wave-1 binding but not by Abi-1 mutants that cannot bind to Wave-1. Moreover, we uncovered an overlapping SNARE domain in the amino terminus of Abi-1 that interacts with Syntaxin-1, a SNARE family member. Further, we demonstrated that Abi-1 shuttles in and out of the nucleus in a leptomycin B (LMB)-dependent manner and that complete nuclear translocation of Abi-1 in the absence of LMB requires the combined inactivation of the SNARE, WAB, and SH3 domains of Abi-1. Thus, Abi-1 undergoes nucleocytoplasmic shuttling and functions at the leading edge to regulate Wave-1 localization and protein levels.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Animals
  • Antigens, Surface / metabolism*
  • Cytoskeletal Proteins / metabolism*
  • Membrane Proteins / metabolism*
  • Mice
  • Microfilament Proteins / metabolism*
  • Molecular Sequence Data
  • NIH 3T3 Cells
  • Nerve Tissue Proteins / metabolism*
  • Protein Structure, Tertiary
  • SNARE Proteins
  • Syntaxin 1
  • Vesicular Transport Proteins*
  • Wiskott-Aldrich Syndrome Protein Family

Substances

  • Abi1 protein, mouse
  • Adaptor Proteins, Signal Transducing
  • Antigens, Surface
  • Cytoskeletal Proteins
  • Membrane Proteins
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • SNARE Proteins
  • Stx1a protein, mouse
  • Syntaxin 1
  • Vesicular Transport Proteins
  • Wasf1 protein, mouse
  • Wiskott-Aldrich Syndrome Protein Family