Practice question

Retrieval pathways restoring escaped ER proteins and itinerant SNAREs rely on COPI coat protein complex I heptamer. COPI subunits alpha, beta, beta prime, gamma, delta, epsilon, zeta assemble 600 kDa coatomer. At Golgi cisternae and ERGIC tubules ARF1-GTP generated by GBF1 GEF recruits en bloc coatomer via gamma-beta-delta trunk interaction. Membrane deformation creates 50-60 nm vesicles containing cargo exposing KKXX or KXKXX dilysine motif at C-terminus binding WD40 propeller of alpha and beta prime COP subunits and KDEL receptor-cargo complexes where receptor tail contains KKXX-like signals. COPII comprising Sec23-24 and Sec13-31 does outward ER to Golgi leg recognizing di-acidic motifs, while clathrin plus AP1 AP2 GGA serves trans-Golgi-to-endosome and plasma-membrane-to-endosome routes sorting via tyrosine and dileucine. AP3 can function with clathrin or as non-clathrin coat for lysosomal membrane proteins. Pharmacologic blockade brefeldin A inhibits ARF GEF collapsing Golgi into ER within minutes by blocking COPI assembly. Hence COPI dedicated retrograde Golgi-to-ER carrier essential for ER proteostasis recycling SNAREs and maintaining Golgi enzyme gradients during cisternal maturation and homeostasis.