DIP/WISH-deficient mice reveal Dia- and N-WASP-interacting protein as a regulator of cytoskeletal dynamics in embryonic fibroblasts.
DIP/WISH binds to mammalian diaphanous and N-WASP, and functions as a scaffold protein by binding to Nck protein (called SPIN90). In addition, DIP/WISH accelerates actin polymerization through integration with N-WASP and is involved in cytoskeletal dynamics. We previously reported that DIP controls the activities of Rho GTPases in a Src-dependent manner, and accordingly contributes to cell motility (Meng et al. 2004). Here, we made the mice lacking DIP/WISH and demonstrated that DIP/WISH is critical for cell motility and adhesion by using murine embryonic fibroblasts (MEF). Rho activity was higher in DIP/WISH-deficient MEF cells even before platelet-derived growth factor (PDGF) or adhesion stimulation. Cell motility and adhesion were impaired in DIP/WISH-deficient MEF cells, and the MEF cells moved little probably due to the deficiency of tail retractions although they had many small membrane ruffles. Consistent with high Rho activity, DIP/WISH-deficient MEF cells exhibited many stress fibers due to clustering pre-existing actin filament. Thus, DIP/WISH is a negative regulator of Rho and modulates cell adhesion by controlling the integration of adhesion molecules.
Section of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki 444-8787, Japan. ttfukumi@hotmail.com
Tomoko
T
Fukumi-Tominaga
Yoshiko
Y
Mori
Atsuko
A
Matsuura
Keiko
K
Kaneko
Makoto
M
Matsui
Masato
M
Ogata
Makoto
M
Tominaga
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D000080865:Formins; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011485:Protein Binding; D022502:Stress Fibers / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C117145:DP-interacting protein, mouse; C491464:Diap1 protein, mouse; D000080865:Formins; D009124:Muscle Proteins; C078332:Nck protein; C426229:Nckipsd protein, mouse; D015513:Oncogene Proteins; D010982:Platelet-Derived Growth Factor; D014157:Transcription Factors; C495772:Wasl protein, mouse; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D049452:Green Fluorescent Proteins; D020741:rho GTP-Binding Proteins