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.
Fukumi-Tominaga
Tomoko
T
Section of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki 444-8787, Japan. ttfukumi@hotmail.com
Mori
Yoshiko
Y
Matsuura
Atsuko
A
Kaneko
Keiko
K
Matsui
Makoto
M
Ogata
Masato
M
Tominaga
Makoto
M
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