Regulation of cell-cell adhesion by Abi/Diaphanous complexes.
Actin polymerization provides the driving force for the formation of cell-cell junctions and is mediated by two types of actin nucleators, Arp2/3 and formins. Proteins required for coordinately linking cadherin-mediated adhesion to Arp2/3-dependent versus formin-dependent nucleation have yet to be defined. Here we show a role for Abi, the Abi-binding partner Nap1, and the Nap1-binding protein Sra1 in the regulation of cadherin-dependent adhesion. We found that Abi, which is known to interact with Wave, leading to activation of the Arp2/3 complex, is also capable of interacting with the Diaphanous (Dia)-related formins in the absence of Wave. Knockdown of Abi, Nap1, Sra1, or Dia markedly inhibited cell-cell junctions, whereas knockdown of Wave or Arp2/3 produced mild and transient phenotypes. Dia and Abi colocalized with beta-catenin at cell-cell junctions. Further, Dia and Wave bound to overlapping sites on Abi1, and Wave competed with Dia for Abi1 binding. Notably, an active Dia1 C-terminal fragment that localizes to cell-cell junctions rescued the abnormal junctions induced by depletion of Abi or Nap1 in epithelial cells. These findings uncover a novel link between cadherin-mediated adhesion and the regulation of actin dynamics through the requirement for an Abi/Dia complex for the formation and stability of cell-cell junctions.
Duke Scholars
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- tRNA Methyltransferases
- Wiskott-Aldrich Syndrome Protein Family
- Time Factors
- Proteins
- Protein Structure, Tertiary
- Protein Binding
- Nuclear Proteins
- Microfilament Proteins
- Mice
- Intercellular Junctions
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- tRNA Methyltransferases
- Wiskott-Aldrich Syndrome Protein Family
- Time Factors
- Proteins
- Protein Structure, Tertiary
- Protein Binding
- Nuclear Proteins
- Microfilament Proteins
- Mice
- Intercellular Junctions