Figure 8.

Model for the sequential action of rab proteins during the endosomal recycling pathway of SLMV-proteins and TfR in nondifferentiated PC12 cells. For reasons of clarity, we refrained from including the plasma membrane derived recycling pathway of SLMVs and the short circuit TfR recycling route. After rab5-dependent endocytosis in clathrin-coated vesicles, SLMV-proteins and TfR codistribute in EE vacuoles (1). Sorting of SLMV-proteins and TfR into distinct recycling tubules does not require the action of rab4 and may occur before or after (2) detachment of the tubules from the EE vacuole. SLMVs and recycling vesicles form through the action of rab4 (3), after which at least part of the newly formed vesicles translocates toward the Golgi area (4), via a pathway that possibly may depend on rab11 as well (5). Fusion of SLMVs with the plasma membrane requires rab3 (6), whereas transport of TfR containing vesicles to the plasma membrane is possibly regulated by rab11 (7).