Chapter 12: Protein Sorting & Vesicular Transport

Protein Sorting & Vesicular Transport establishes the foundational secretory pathway, detailing how proteins destined for secretion, the plasma membrane, or specific organelles are initially targeted to the ER via N-terminal signal sequences, signal recognition particles (SRP), and the translocon complex, typically during cotranslational translocation. The text distinguishes between the rough ER, which is the site of protein synthesis, folding, and post-translational modifications such as N-linked glycosylation, disulfide bond formation, and GPI anchor addition, and the smooth ER, which is vital for lipid metabolism, phospholipid synthesis, and detoxification. Significant attention is given to quality control mechanisms, including the unfolded protein response (UPR) and ER-associated degradation (ERAD), which ensure that only correctly folded proteins proceed through the pathway. The narrative tracks the movement of cargo via vesicular transport, explaining the specific roles of coat proteins—COPII for anterograde transport, COPI for retrograde retrieval, and clathrin for transport from the trans-Golgi network—along with the molecular machinery of vesicle budding and fusion regulated by GTP-binding proteins, Rab proteins, and SNARE complexes. Within the Golgi apparatus, the chapter describes the ordered processing of glycoproteins, including O-linked glycosylation and the synthesis of sphingomyelin and complex cell wall polysaccharides in plants, leading to sorting events in the trans-Golgi network for constitutive or regulated secretion. Finally, the text explores the digestive functions of lysosomes, characterized by their acidic pH and acid hydrolases, explaining the targeting of lysosomal enzymes via mannose-6-phosphate tagging, the pathogenesis of lysosomal storage diseases like Gaucher disease, and the organelle's role in autophagy and the turnover of cellular components.