Determination of the RhoPDE transmembrane topology and orientation. Immobilized COS-7 cells were transfected with the dual (C8 and 1D4) epitope-tagged RhoPDE on glass coverslips and incubated with the antibodies under permeabilized or unpermeabilized conditions for immunofluorescent staining, as indicated in the figure and described in Experimental Procedures. Panels A and B show intact and detergent-permeabilized cells, respectively, probed with the 1D4 antibody. Panels C and D show intact and detergent-permeabilized cells, respectively, probed with the C8 antibody. Fluorescence from either probe is observed only in permeabilized cells, indicating both epitopes are intracellular. The COS-7 cells in panels B and D show a diffuse staining pattern typical of proteins localized to the plasma membrane.