Article

RhoB affects macrophage adhesion, integrin expression and migration

Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine, London, UK.
Experimental Cell Research (Impact Factor: 3.37). 11/2007; 313(16):3505-16. DOI: 10.1016/j.yexcr.2007.07.014
Source: PubMed

ABSTRACT Rho GTPases regulate multiple cellular responses, including cell motility and cell cycle progression. The Rho isoform RhoB represses transformation and affects endosomal trafficking, but its effects on cell adhesion and migration have not been investigated in detail. Here we show that RhoB-null macrophages are more rounded than wild-type macrophages on fibronectin and uncoated glass, and have reduced adhesion to ICAM-1 and glass but not fibronectin. This correlated with lower cell surface expression of beta2 and beta3 integrins but not beta1 integrin. RhoB-null cells migrated faster than Wt cells on fibronectin, consistent with their smaller spread area, but slower than Wt cells on glass, reflecting their reduced adhesion. C3 transferase, which inhibits RhoA, RhoB and RhoC, induced cell spreading but this effect was reduced in RhoB-null cells. However, RhoB is not required for assembly of podosomes, which are integrin-based adhesion sites, whereas C3 transferase induced a decrease in podosomes and defects in tail retraction. Since macrophages do not express RhoC, these effects of C3 transferase are due to inhibition of RhoA rather than RhoB. Our results suggest that RhoB affects cell shape and migration by regulating surface integrin levels.

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    • "macrophages, RhoB has been postulated to affect adhesion by affecting surface levels of b-integrins (Wheeler and Ridley, 2007). We demonstrate that RhoB mediates ATF-induced upregulation of surface integrin levels, explaining how RhoB specifically affects uPAR responses, and hence uPAR-dependent signalling. "
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    • "The work of several laboratories has identified important roles for RhoB in the endocytic trafficking of RTKs, such as EGFR and PDGFR, along with key downstream signaling molecules Src, Akt and ERK [Adini et al., 2003; Huang et al., 2007; Sandilands et al., 2004; Wherlock et al., 2004]. A study on macrophages has reported that RhoB affects cell adhesion and migration on different substrates in response to colony stimulating factor-1 (CSF-1) stimulation by regulating cell surface expression of integrins [Wheeler and Ridley, 2007]. However, the role of RhoB in growth factor induced cell migration has not been studied in detail. "
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    • "In macrophages, Rho B inactivation results in decreased surface expression of integrins ␤2 and ␤3, whereas ␤1 surface expression remains constant. However, modification of this integrin pattern does not affect podosome formation (Wheeler and Ridley, 2007). In contrast, the importance of ␤1 in invadopodia was suggested by activation of these integrins by soluble antibody, which leads to an increase in ECM degradation (Nakahara et al., 1998). "
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