Neural Wiskott-Aldrich syndrome protein is involved in hepatocyte growth factor-induced migration, invasion, and tubulogenesis of epithelial cells.
Neural Wiskott-Aldrich syndrome protein (N-WASP), a member of the WASP family, regulates reorganization of the actin cytoskeleton through activation of the Arp2/3 complex. To date, most studies of N-WASP have focused on intracellular and morphological phenomena, such as vesicle transport and filopodium formation. We investigated the importance of N-WASP in epithelial morphogenesis, using Madin-Darby canine kidney epithelial cells, which form branching tubules when cultured with hepatocyte growth factor (HGF) in collagen gel. We established MDCK cell lines that overexpress wild-type N-WASP (WT-NW) or a dominant-negative form of N-WASP (DN-NW). WT-NW and parental Madin-Darby canine kidney cells formed branching tubules in collagen gel in response to HGF. However, formation of branching tubules was suppressed in DN-NW cells. During tubulogenesis, endogenous N-WASP accumulated at cell extensions protruding from the walls of the cysts and at the tips of the extending tubules. Gross cell morphology, cell-cell adhesion, cell polarity, and scattering in response to HGF were unaffected in WT-NW and DN-NW cells. In contrast, directed cell migration and HGF-induced invasion were significantly repressed in DN-NW cells. These results indicate that N-WASP regulates HGF-induced cell migration and invasion, which are required for epithelial tubulogenesis.
Yamaguchi
Hideki
H
Division of Biochemistry, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Miki
Hiroaki
H
Takenawa
Tadaomi
T
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000502:physiology*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal
D009419:Nerve Tissue Proteins; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D017228:Hepatocyte Growth Factor