Chapter 14: Vesicular Traffic, Secretion & Endocytosis

The core mechanism of vesicular transport is established as a conserved process involving vesicle budding, cargo selection, and fusion. Key molecular players include small GTPases like Sar1 and ARF that regulate coat assembly, and coat proteins such as COPII, COPI, and clathrin that shape the vesicle and select cargo via sorting signals. COPII vesicles facilitate anterograde transport from the Endoplasmic Reticulum (ER) to the cis-Golgi, while COPI vesicles mediate retrograde transport, retrieving ER-resident proteins bearing KDEL or KKXX signals. The text explains the dynamic nature of the Golgi through the cisternal maturation model, where cisternae progress from cis to trans while enzymes are recycled backward. From the trans-Golgi network (TGN), proteins are sorted to various destinations. Soluble lysosomal enzymes are targeted via the Mannose 6-Phosphate (M6P) signal, recognized by M6P receptors that package them into clathrin-coated vesicles; defects in this pathway lead to lysosomal storage disorders like I-cell disease. The chapter further distinguishes between constitutive secretion, which operates continuously, and regulated secretion, where proteins like insulin are stored in secretory granules until a signal triggers exocytosis. In polarized epithelial cells, distinct mechanisms sort proteins to apical or basolateral domains, sometimes involving transcytosis. Receptor-mediated endocytosis is thoroughly examined using the Low-Density Lipoprotein (LDL) receptor as a model, highlighting how the NPXY sorting signal recruits clathrin/AP2 complexes and how endosomal acidification drives ligand dissociation. The discussion extends to the downregulation of signaling receptors like EGFR and the formation of multivesicular bodies (MVBs) for degrading membrane proteins. This process relies on ubiquitin tagging and the ESCRT machinery, which is notably exploited by retroviruses like HIV for budding. Finally, the chapter covers autophagy, a survival mechanism where cytoplasmic contents are engulfed in double-membrane autophagosomes for lysosomal degradation, regulated by Atg proteins during starvation or quality control.