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.
Ryu
Jae Ryun
JR
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Box 3813, Durham, North Carolina 27710, USA.
Echarri
Asier
A
Li
Ran
R
Pendergast
Ann Marie
AM
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D004285:Dogs; D005326:Fetal Proteins / Q000378:metabolism; D000080865:Formins; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D013997:Time Factors; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism; D012359:tRNA Methyltransferases
C513733:ABI1 protein, human; C096831:ABI2 protein, human; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C108962:DIAPH1 protein, human; C491462:DIAPH2 protein, human; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D011506:Proteins; D051300:Wiskott-Aldrich Syndrome Protein Family; C498548:TRMO protein, human; D012359:tRNA Methyltransferases