Practice question

Classical secretory pathway described by George Palade using pulse-chase autoradiography follows polarized itinerary from synthesis to release. Proteins destined for secretion start on rough ER where N-terminal signal peptide directs co-translational insertion via Sec61 channel and cleavage by signal peptidase. Core N-glycosylation, chaperone assisted folding and disulfide formation occur there before concentration at ER exit sites organized by Sec16 and COPII coat assembly controlled by Sar1 GTPase. Vesicles form ER-Golgi intermediate compartment and fuse into cis-Golgi cisterna. Cargo then traverses Golgi stack cis to trans via cisternal maturation while Golgi glycosyltransferases, sulfotransferases, mannosidases and processing proteases like furin modify glycans and cleave propeptides sequentially. At trans-Golgi network, sorting receptors sortilin, sortilin-related and mannose-6-phosphate receptors divert lysosomal enzymes, while remaining cargo enters constitutive secretory vesicles or regulated dense core granules controlled by cargo receptors and calcium. SNARE proteins including VAMP, syntaxin and SNAP drive final fusion with plasma membrane releasing contents. This ER to Golgi to plasma membrane axis explains sensitivity to brefeldin A and requirement for ER quality control before export and extracellular deposition.