Arp2/3 activity is necessary for efficient formation of E-cadherin adhesive contacts.
Classical cadherin adhesion molecules are fundamental determinants of cell-cell recognition that function in cooperation with the actin cytoskeleton. Productive cadherin-based cell recognition is characterized by a distinct morphological process of contact zone extension, where limited initial points of adhesion are progressively expanded into broad zones of contact. We recently demonstrated that E-cadherin ligation recruits the Arp2/3 actin nucleator complex to the plasma membrane in regions where cell contacts are undergoing protrusion and extension. This suggested that Arp2/3 might generate the protrusive forces necessary for cell surfaces to extend upon one another during contact assembly. We tested this hypothesis in mammalian cells by exogenously expressing the CA region of N-WASP. This fragment, which potently inhibits Arp2/3-mediated actin assembly in vitro, also effectively reduced actin assembly at cadherin adhesive contacts. Blocking Arp2/3 activity by this strategy profoundly reduced the ability of cells to extend cadherin adhesive contacts but did not affect cell adhesiveness. These findings demonstrate that Arp2/3 activity is necessary for cells to efficiently extend and assemble cadherin-based adhesive contacts.
Verma
Suzie
S
Institute for Molecular Bioscience, School for Biomedical Science, The University of Queensland, St. Lucia, Queensland 4072, Australia.
Shewan
Annette M
AM
Scott
Jeanie A
JA
Helwani
Falak M
FM
den Elzen
Nicole R
NR
Miki
Hiroaki
H
Takenawa
Tadaomi
T
Yap
Alpha S
AS
D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D007376:Interleukin-2; D015850:Interleukin-6; D051379:Mice; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins; D014162:Transfection; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal
C495926:ACTR2 protein, human; C495928:ACTR3 protein, human; D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins; C495927:Actr2 protein, mouse; C495929:Actr3 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; D007376:Interleukin-2; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C495771:WASL protein, human; C495772:Wasl protein, mouse; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; C089276:recombinant fusion protein IL-6 - IL-2