RHOGDI-GAMMA - A GDP-DISSOCIATION INHIBITOR FOR RHO-PROTEINS WITH PREFERENTIAL EXPRESSION IN BRAIN AND PANCREAS

GDP-dissociation inhibitors (GDIs) play a primary role in modulating t he activation of GTPases and may also be critical for the cellular com partmentalization of GTPases, RhoGDI and GDI/D4 are two currently know n GDIs for the Rho-subfamily of GTPases, Using their cDNAs to screen a human brain cDNA library under low stringency, we have cloned a homol ogous cDNA preferentially expressed at high levels in brain and pancre as, The predicted protein, named RhoGDI gamma, is approximate to 50% i dentical to GDI/D4 and RhoGDI, It binds to CDC42 and RhoA with less af finity compared with RhoGDI and does not bind with Rac1, Rac2, or Ras, RhoGDI gamma functions as a GDI for CDC42 but with approximate to 20 times less efficiency than RhoGDI, Immunohistochemical studies showed a diffuse punctate distribution of the protein in the cytoplasm with c oncentration around the nucleus in cytoplasmic vesicles, Overexpressio n of the protein in baby hamster kidney cells caused the cells to roun d up with loss of stress fibers, A distinct hydrophobic amino terminus in RhoGDI gamma, not seen in the other two RhoGDIs, could provide a m echanism for localization of the GDI to specific membranous compartmen t thus determining function distinct from RhoGDI or GDI/D4, Our result s provide evidence that there is a family of GDIs for the Rho-related GTPases and that they differ in binding affinity, target specificity, and tissue expression, We propose that RhoGDI be renamed RhoGDI alpha and GDID4 be renamed RhoGDI beta, The new GDI should widen the scope o f investigation of this important class of regulatory protein.