RhoGDI: multiple functions in the regulation of Rho family GTPase activities.
RhoGDI (Rho GDP-dissociation inhibitor) was identified as a down-regulator of Rho family GTPases typified by its ability to prevent nucleotide exchange and membrane association. Structural studies on GTPase-RhoGDI complexes, in combination with biochemical and cell biological results, have provided insight as to how RhoGDI exerts its effects on nucleotide binding, the membrane association-dissociation cycling of the GTPase and how these activities are controlled. Despite the initial negative roles attributed to RhoGDI, recent evidence has come to suggest that it may also act as a positive regulator necessary for the correct targeting and regulation of Rho activities by conferring cues for spatial restriction, guidance and availability to effectors. These potential functions are discussed in the context of RhoGDI-associated multimolecular complexes, the newly emerged shuttling capability and the importance of the particular membrane microenvironment that represents the site of action for GTPases. All these results point to a wider role for RhoGDI than initially perceived, making it a binding partner that can tightly control Rho GTPases, but which also allows them to reach their full spectrum of activities.
Dovas
Athanassios
A
Division of Biomedical Sciences, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
Couchman
John R
JR
D000595:Amino Acid Sequence; D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000737:chemistry* / Q000502:physiology*; D008969:Molecular Sequence Data; D005810:Multigene Family; D011487:Protein Conformation; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
D020730:Guanine Nucleotide Dissociation Inhibitors; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D020741:rho GTP-Binding Proteins