Rac1 and Rac2 regulate macrophage morphology but are not essential for migration.
Rac GTPases are believed to contribute to migration in leukocytes by transducing signals from cell surface receptors to the actin and microtubule cytoskeletons. Mammals have three closely related Rac isoforms, Rac1, Rac2 and Rac3, and it is widely assumed that cell migration requires the activity of these Rac GTPases. We have previously shown that Rac1-null mouse macrophages have altered cell shape and reduced membrane ruffling but normal migration speed. Here we investigate the behaviour of macrophages lacking Rac2 (Rac2(-/-)) or Rac1 and Rac2 (Rac1/2(-/-)). Rac2(-/-) macrophages have reduced F-actin levels and lack podosomes, which are integrin-based adhesion sites, and their migration speed is similar to or slightly slower than wild-type macrophages, depending on the substrate. Unexpectedly, Rac1/2(-/-) macrophages, which do not express Rac1, Rac2 or Rac3, migrate at a similar speed to wild-type macrophages on a variety of substrates and perform chemotaxis normally, although their morphology and mode of migration is altered. However, Rac1(-/-) and Rac1/2(-/-) but not Rac2(-/-) macrophages are impaired in their ability to invade through Matrigel. Together, these data show that Rac1 and Rac2 have distinct roles in regulating cell morphology, migration and invasion, but are not essential for macrophage migration or chemotaxis.
Wheeler
Ann P
AP
Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine, 91 Riding House Street, London, W1W 7BS, UK.
Wells
Claire M
CM
Smith
Stephen D
SD
Vega
Francisco M
FM
Henderson
Robert B
RB
Tybulewicz
Victor L
VL
Ridley
Anne J
AJ
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000235:genetics; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D005353:Fibronectins / Q000494:pharmacology; D007797:Laminin / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis / Q000502:physiology*; D009479:Neuropeptides / Q000172:deficiency / Q000502:physiology*; D011509:Proteoglycans / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism / Q000502:physiology; D017384:Sequence Deletion; D020744:rac GTP-Binding Proteins / Q000172:deficiency / Q000502:physiology*; D020830:rac1 GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein
D003094:Collagen; D004338:Drug Combinations; D005353:Fibronectins; D007797:Laminin; D009479:Neuropeptides; D011509:Proteoglycans; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein; C484602:Rac1 protein, mouse; C059485:matrigel