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J. Cell Biol.,
Volume 141, Number 5, June 1, 1998 1147-1157
§
* Muscle and Motility Research Centre ( Three members of the Rho family, Cdc42,
Rac, and Rho are known to regulate the organization of
actin-based cytoskeletal structures. In Bac1.2F5 macrophages, we have shown that Rho regulates cell contraction, whereas Rac and Cdc42 regulate the formation of lamellipodia and filopodia, respectively. We
have now tested the roles of Cdc42, Rac, and Rho in
colony stimulating factor-1 (CSF-1)-induced macrophage migration and chemotaxis using the Dunn
chemotaxis chamber. Microinjection of constitutively
activated RhoA, Rac1, or Cdc42 inhibited cell migration, presumably because the cells were unable to polarize significantly in response to CSF-1. Both Rho and
Rac were required for CSF-1-induced migration, since
migration speed was reduced to background levels in
cells injected with C3 transferase, an inhibitor of Rho,
or with the dominant-negative Rac mutant, N17Rac1. In contrast, cells injected with the dominant-negative
Cdc42 mutant, N17Cdc42, were able to migrate but did
not polarize in the direction of the gradient, and
chemotaxis towards CSF-1 was abolished.
We conclude that Rho and Rac are required for the
process of cell migration, whereas Cdc42 is required for
cells to respond to a gradient of CSF-1 but is not essential for cell locomotion.
M.R.C. Unit), The Randall Institute, King's College London WC2B 5RL; The Ludwig
Institute for Cancer Research, London W1P 8BT; and § Department of Biochemistry and Molecular Biology, University College
London WC1E 6BT, United Kingdom
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