POSTTRANSLATION

Part of “CHAPTER 3 – BIOSYNTHESIS AND SECRETION OF PEPTIDE HORMONES“

Up to the translational and cotranslational steps in the ER, all secretory, membrane, lysosome, endogenous ER, and Golgi proteins have traversed the same biosynthetic path. After this point, the major task of sorting and transferring the proteins to the correct intracellular destinations must be completed. This complex process occurs in the Golgi stack and requires sorting signals among the proteins and sorting mechanisms in this organelle. A polypeptide hormone destined for regulated secretion must exit the ER, traverse the Golgi stack, and arrive properly in the secretory granule (Fig. 3-12).

FIGURE 3-12. The polypeptide hormone highway. Protein hormone synthesis is initiated in the cytoplasm on polyribosomes. The partially processed hormone, with the signal peptide removed and N-linked carbohydrate moieties attached and with appropriate folding, enters the lumen of the rough endoplasmic reticulum (RER). By way of transport vesicle–transitional elements, these partially processed products are transferred to the Golgi stack on fusion and release. In a serial process of budding formation of secretory vesicles and fusion, processed products are transferred through the Golgi stack, from which they exit as secretory vesicles or granules after sorting in the trans and trans-Golgi network compartments of the Golgi. Materials are then released from granules by the fusion of vesicles or granules with the plasma membrane.

The Golgi stack comprises a series of flattened, saccular membranous compartments that encompass four histologically and functionally distinct regions: the cis, medial, and trans regions of the Golgi complex and the trans-Golgi network (TGN)43,44 (Fig. 3-13). The cis-Golgi region is most proximal to the transitional elements of the RER, and the TGN is most distal. The maintenance of distinct Golgi-specific antigens, unique enzyme markers, and different lectin-binding characteristics suggest that the compartments are not contiguous.

FIGURE 3-13. The Golgi stack. The Golgi stack consists of numerous membranous compartments, including cis, medial, and trans-Golgi elements. These compartments may be differentiated by the presence of specific enzymes. Partially processed protein hormones traverse this system by way of intermediate secretory vesicles in a budding-fusion reiterative process. In addition to transport, protein processing occurs. Sorting with routing to ultimate destinations in cellular sites is accomplished in the trans-Golgi network (TGN). Secretory peptides may be sorted to constitutive or regulated secretory pathways. Constitutive secretory pathways are equivalent to the pathways taken by membrane proteins, whereby non–clathrin-coated membrane segments are used. The regulated secretory-secretory granule pathway involves a clathrin-coated pit among membrane segments. This is similar to the pathway taken by lysosomal components. (Adapted from Griffiths G, Simons K. The trans Golgi network: sorting at the exit site of the Golgi complex. Science 1986; 234:438.)

A vesicle transfer model has been proposed to account for transport of materials from the RER to the TGN. In this model, membrane vesicles form from the upstream compartment by budding at the rims of the Golgi plates and rejoin the adjacent downstream compartment by vesicle fusion and the interaction of microfilaments. The reiterative process of budding and fusion of secretory or transport vesicles causes vectorial transfer of proteins from the RER to the TGN in a unidirectional and energy-dependent process.

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