Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Adhesion / drug effects
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Cell Movement / drug effects
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Cells, Cultured
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Cytoskeleton / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Embryo, Mammalian / cytology
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Fibroblasts / cytology
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Fibroblasts / metabolism*
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Formins
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Kinetics
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Mice
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Mice, Inbred C57BL
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Mice, Inbred Strains
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Mice, Knockout
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Microscopy, Confocal
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Muscle Proteins / genetics
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Muscle Proteins / metabolism*
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Oncogene Proteins / genetics
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Oncogene Proteins / metabolism
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Platelet-Derived Growth Factor / pharmacology
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Protein Binding
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Stress Fibers / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Wiskott-Aldrich Syndrome Protein, Neuronal / genetics
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Wiskott-Aldrich Syndrome Protein, Neuronal / metabolism*
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rho GTP-Binding Proteins / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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DNA-Binding Proteins
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DP-interacting protein, mouse
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Diap1 protein, mouse
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Formins
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Muscle Proteins
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Nck protein
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Nckipsd protein, mouse
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Oncogene Proteins
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Platelet-Derived Growth Factor
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Transcription Factors
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Wasl protein, mouse
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Wiskott-Aldrich Syndrome Protein, Neuronal
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Green Fluorescent Proteins
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rho GTP-Binding Proteins