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The ABCs of GTPase Activity

Physiological regulation of some GTPases requires three supporting players: guanine nucleotide exchange factors (GEFs) to replace bound GDP with GTP, GTPase-activating proteins (GAPs) to accelerate hydrolysis of bound GTP, and guanine nucleotide dissociation inhibitors (GDIs) to transport and insert GTPases into the membrane. How the activities of these three regulators are coordinated is still incompletely understood.

Model of Bcr-RhoGDI interaction.

In this Paper of the Week, Soo-Mi Kweon and colleagues re-examined GTPase interactions using immunoprecipitation assays and found unexpectedly that RhoGDI can form a protein complex with Bcr, an important GAP for the GTPase Rac, in vivo, an interaction that inhibits Bcr from converting Rac-GTP to Rac-GDP. Noteworthy was that the binding occurred between the C-terminal domain of RhoGDI, which does not bind Rac, and the GAP domain of Bcr, which does bind Rac. Addition of either permanently GTP-bound Rac or a hydrolysis-deficient Bcr mutant decreased the levels of Bcr-Rho binding, whereas Rac-GDP caused no interference, evidence that Rho- and Rac-GTP compete for exclusive Bcr binding. Kweon and colleagues suggest that the Bcr-Rho interaction may serve to deliver newly generated Rac-GDP directly to Rho or act as a regulator to prevent unnecessary Rac-GTP hydrolysis.

FOOTNOTES

See referenced article, J. Biol. Chem. 2008, 283, 3023-3030

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