Practice question

Coat identity determines vesicle origin and destination providing directional logic to secretory pathway. COPII composed of Sar1 initiating curvature, inner adaptor Sec23-Sec24 binding cargo export signals, outer cage Sec13-Sec31 polymerizing into cuboctahedron operates exclusively at ER exit sites producing vesicles moving toward ERGIC and cis-Golgi carrying newly synthesized secretory proteins bearing ER exit motifs DXE, LXXLE. COPI composed of ARF1-GTP and heptameric coatomer operates reciprocally at Golgi rims and ERGIC retrieving material backward including KKXX membrane proteins and KDEL receptor bound luminal chaperones. Clathrin triskelia with heterotetrameric adaptors AP1 at TGN, AP2 at plasma membrane, GGAs and AP3 operates at later stations where PI4P or PI(4,5)P2 and ARF family GTPases recruit adaptors: TGN to late endosomes for mannose-6-phosphate receptor bound hydrolases, plasma membrane to early endosomes for transferrin uptake, and endosomes to lysosomes. Thus ER to Golgi uniquely COPII dependent mechanistically independent of clathrin lattice. siRNA of clathrin heavy chain blocks transferrin endocytosis and cathepsin D sorting but not ER export of temperature-sensitive VSV-G, while Sec24B depletion arrests ER exit confirming distinct machinery division and functional separation.