Endocytic sorting pathways pathway

In a simplified view, the total flow is as follows (Fig. 8). Both soluble and membrane proteins that are translated at the membrane-bound ribosome are first localized at the ER. Some of them are transported to the Golgi apparatus, whereas others remain at the ER. At the Golgi apparatus, including the trans Golgi network (TGN), the next selection occurs some are transported to the plasma membrane, others to the endosome and to the lysosome/vacuole finally, and still others remain there. The lysosome is also an important organelle for the other transport system, the endocytic pathway. In this pathway, proteins at the plasma membrane are internalized by endocytosis. The sorting to lysosomes is treated in the next section. 

A nonubiquitous organelle, the melanosome, is specialized for melanin synthesis. It is somewhat similar to the lysosome, and the resident proteins are derived from the endocytic pathway. A sorting signal, the NQPLLT, was found in the cytoplasmic protein of a human membrane protein (Vijayasaradhi et al., 1995). 

Many cells have an asymmetric structure because of the necessity for function (Drubin and Nelson, 1996). For example, (the outer surface of) the plasma membrane of epithelial cells is fenced by a tight junction so that the lipids are separated between the apical part and the basolateral part (Fig. 9) (Eaton and Simons, 1995). Therefore, some molecular mechanisms must exist to sort the plasma membrane proteins into these two parts. Some signals related to the secretory/endocytic pathways have been found important (Matter and Mellman, 1994). Their details are not described here because the area is too specific for predictive purposes. 

Le Borgne, R., and Hoflack, B. (1998a). Mechanisms of protein sorting and coat assembly insights from the clathrin-coated vesicle pathway. Curr. Opin. Cell Biol. 10, 499-503. Le Borgne, R., and Hoflack, B. (1998b). Protein transport from the secretory to the endocytic pathway in mammalian cells. Biochim. Biophys. Acta 1404, 195-209. 

Amerik, a. Y., Nowak, J., SwAMiNATHAN, S., and Hochstrasser, M. The Doa4 deubiquitinating enzyme is functionally linked to the vacuolar protein-sorting and endocytic pathways. Mol Biol Cell, 2000, 11, 3365-80. 

Early endosomes are the main sorting station in the endocytic pathway. In their acidic interior (pH 5.9-6.0), the receptor and its ligand can be released. The receptor may be recycled to the surface by vesicles that fuse with the plasma membrane. Material that cannot escape from the early endosomes is further transported via multivesicular bodies to late endosomes and digesting lysosomes that contain a broad spectrum of peptidases and hydrolases in an acidic surrounding [for reviews on endocytosis see Refs. (10-12), for review on clathrin uptake see Refs. (9,13)]. 

Specihc membrane and membrane-associated proteins also control the organelle traffic and fusion events that are associated with the movement of proteins between different intracellular compartments. Membrane proteins of the secretory and endocytic pathways depend on sorting signals that reside in their cytoplasmic domains. Many proteins exhibit multiple signals that determine their passage along these diverse pathways. Therefore, the steady-state distribution of any given membrane... 

FIGURE 17-1 Overview of the secretory and endocytic pathways of protein sorting. 

The endocytic pathway delivers some ligands (e.g., LDL particles) to lysosomes where they are degraded. Most receptor-ligand complexes dissociate in the acidic milieu of the late endosome the receptors are recycled to the plasma membrane, while the ligands are sorted to lysosomes (see Figure 17-28). 

Wessling-Resnick, M., and Braell, W. A., 1990, The sorting and segregation mechanism ofthe endocytic pathway is functional in a cell-free system, J. Biol Chem. 265 690-699. 

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