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Figure 3. Proposed regulation of protein recycling through the ERC by PS/
-secretase. Transferrin (red) is internalized from the plasma membrane into primary endosomes, which fuse with sorting endosomes. These tubular vesicular structures target proteins to late endosomes and lysosomes for degradation or alternatively back to the plasma membrane via the ERC. The ERC is a collection of tubular organelles associated with microtubules. APP (green) and many other type I membrane proteins, some of which are substrates for PS/-secretase, undergo internalization and recycling back to the plasma membrane via the ERC. Our results propose that PS/-secretase activity is essential for correct protein recycling via the ERC, and that in the absence of PS/-secretase activity, proteins are unable to exit the ERC or their exit is slowed down. This results in protein accumulation in the ERC, as indicated by our data. Alternatively, accumulation of CTFs in the absence of PS/-secretase activity may delay protein clearance from the ERC.
