RHOA is activated by guanine nucleotide exchange factors (RhoGEFs), exchanging GDP for GTP. RHOA, activated following binding of MDGIs (RTN4, MAG or OMG) to the complex of NOGO receptor (RTN4R, also known as NgR) and NGFR (p75NTR), rigidifies the actin cytoskeleton, thereby inhibiting axonal elongation and causing growth cone collapse. MCF2 (Dbl) RHO GEF was used to demonstrate activation of RHOA downstream of NGFR and RTN4R-mediated sequestration of ARHGDIA, a RHO-GDI, but other RHO GEFs may also be involved in RHOA activation (Yamashita and Tohyama 2003).