The Ras-related protein Cdc42Hs and bradykinin promote formation of peripheral actin microspikes and filopodia in Swiss 3T3 fibroblasts

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Mol. Cell. Biol., 04 1995, 1942-1952, Vol 15, No. 4
Copyright © 1995, American Society for Microbiology

The Ras-related protein Cdc42Hs and bradykinin promote formation of peripheral actin microspikes and filopodia in Swiss 3T3 fibroblasts

R Kozma, S Ahmed, A Best and L Lim
Institute of Neurology, London, United Kingdom.

The Ras-related protein Cdc42 plays a role in yeast cell budding and polarity. Two related proteins, Rac1 and RhoA, promote formation in mammalian cells of membrane ruffles and stress fibers, respectively, which contain actin microfilaments. We now show that microinjection of the related human Cdc42Hs into Swiss 3T3 fibroblasts induced the formation of peripheral actin microspikes, determined by staining with phalloidin. A proportion of these microspikes was found to be components of filopodia, as analyzed by time-lapse phase-contrast microscopy. The formation of filopodia was also found to be promoted by Cdc42Hs microinjection. This was followed by activation of Rac1- mediated membrane ruffling. Treatment with bradykinin also promoted formation of microspikes and filopodia as well as subsequent effects similar to that seen upon Cdc42Hs microinjection. These effects of bradykinin were specifically inhibited by prior microinjection of dominant negative Cdc42HsT17N, suggesting that bradykinin acts by activating cellular Cdc42Hs. Since filopodia have been ascribed an important sensory function in fibroblasts and are required for guidance of neuronal growth cones, these results indicate that Cdc42Hs plays an important role in determining mammalian cell morphology.

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Kulkarni, S., Goll, D. E., Fox, J. E. B. (2002). Calpain Cleaves RhoA Generating a Dominant-negative Form That Inhibits Integrin-induced Actin Filament Assembly and Cell Spreading. J. Biol. Chem. 277: 24435-24441 [Abstract] [Full Text]
Swart-Mataraza, J. M., Li, Z., Sacks, D. B. (2002). IQGAP1 Is a Component of Cdc42 Signaling to the Cytoskeleton. J. Biol. Chem. 277: 24753-24763 [Abstract] [Full Text]
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Kanazawa, H., Ohsawa, K., Sasaki, Y., Kohsaka, S., Imai, Y. (2002). Macrophage/Microglia-specific Protein Iba1 Enhances Membrane Ruffling and Rac Activation via Phospholipase C-gamma -dependent Pathway. J. Biol. Chem. 277: 20026-20032 [Abstract] [Full Text]
Brown, M. C., West, K. A., Turner, C. E. (2002). Paxillin-dependent Paxillin Kinase Linker and p21-Activated Kinase Localization to Focal Adhesions Involves a Multistep Activation Pathway. Mol. Biol. Cell 13: 1550-1565 [Abstract] [Full Text]
Li, X., Saint-Cyr-Proulx, E., Aktories, K., Lamarche-Vane, N. (2002). Rac1 and Cdc42 but Not RhoA or Rho Kinase Activities Are Required for Neurite Outgrowth Induced by the Netrin-1 Receptor DCC (Deleted in Colorectal Cancer) in N1E-115 Neuroblastoma Cells. J. Biol. Chem. 277: 15207-15214 [Abstract] [Full Text]
Krebs, A., Rothkegel, M., Klar, M., Jockusch, B. M. (2002). Characterization of functional domains of mDia1, a link between the small GTPase Rho and the actin cytoskeleton. J. Cell Sci. 114: 3663-3672 [Abstract] [Full Text]
Woodring, P. J., Litwack, E. D., O'Leary, D. D.M., Lucero, G. R., Wang, J. Y.J., Hunter, T. (2002). Modulation of the F-actin cytoskeleton by c-Abl tyrosine kinase in cell spreading and neurite extension. J. Cell Biol. 156: 879-892 [Abstract] [Full Text]
Furman, C., Short, S. M., Subramanian, R. R., Zetter, B. R., Roberts, T. M. (2002). DEF-1/ASAP1 Is a GTPase-activating Protein (GAP) for ARF1 That Enhances Cell Motility through a GAP-dependent Mechanism. J. Biol. Chem. 277: 7962-7969 [Abstract] [Full Text]

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