The C-terminal cytoplasmic domain of DOR contains an autonomous intracellular targeting signal. A, Stably transfected PC12 cells expressing a FLAG-tagged chimeric MOR containing divergent residues from the distal cytoplasmic tail of DOR (residues 345–372) were incubated in the absence (Control) or presence (NGF) of NGF (100 ng/ml) for 1 hr, fixed, and processed for immunocytochemical staining. Representative micrographs of receptor localization in control and NGF-treated cells are shown. B, Quantitative analysis of coded specimens corresponding to the experiment illustrated in A, as well as in cells incubated with NGF for 5 d (as in Fig. 1), was conducted as described above, and data represent means ± SEM from three independent experiments. C, PC12 cells were transiently transfected with an expression construct encoding CD4 or the CD4-DOR tail fusion, as described in Materials and Methods. Forty-eight hours after transfection, cells were incubated in the absence or presence of 100 ng/ml NGF for 1 hr, and then cells were fixed, and CD4 proteins were localized using anti-CD4 antibody. Confocal optical sections (∼0.5 μm thick) taken through the centers of cells are shown. D, Quantitative analysis of the results described in C. Bars represent means ± SEM from three independent experiments, each involving blinded analysis of ∼100 cells selected at random per condition.