Skip to content
Login Register

#COPI

3 public questions tagged with this topic.

Protein Sorting and Trafficking

Which of the following does NOT require clathrin-coated vesicles?

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.

Ref: Alberts et al., MBC: COPII ER-to-Golgi transport does not require clathrin coats.

View Details
Protein Sorting and Trafficking

Which coat protein mediates retrograde transport from the Golgi to ER?

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.

Ref: Alberts et al., MBC: COPI coat mediates retrograde Golgi-to-ER transport and retrieval.

View Details
Protein Sorting and Trafficking

The primary function of coat proteins like COPI and COPII is:

Formation of transport vesicles requires peripheral coat proteins that deform donor membrane into bud and select cargo through direct recognition of sorting motifs. COPII coat assembly initiates when Sar1 activated by Sec12 GEF at ER exit sites embeds N-terminal amphipathic helix into ER membrane, recruiting Sec23-Sec24 heterodimer where Sec24 contains multiple cargo-binding sites for di-acidic Asp-X-Glu, di-phenylalanine and motifs presented by cargo receptors like ERGIC-53 and p24 family. Outer layer Sec13-Sec31 forms cuboctahedral cage providing curvature and scaffold. COPI coat activated by Arf1-GTP after GBF1 and BIG GEFs acts at Golgi and ERGIC: Arf1 exposes myristoylated helix, recruits coatomer complex α, β, β', γ, δ, ε, ζ recognizing KKXX retrieval signals on ER residents and KDEL receptor-cargo complexes. Both coats polymerize, deform membrane, concentrate cargo and then disassemble after GAP-stimulated GTP hydrolysis enabling fusion. Nuclear import receptors, microtubule depolymerization dynamics or mitochondrial ATP synthesis do not involve COPI/COPII, emphasizing their specific role in early secretory pathway vesicle formation, fidelity of forward transport and recycling to maintain compartmental protein composition and prevent secretion of ER chaperones and enzymes.

Ref: Alberts et al., Molecular Biology of the Cell, 6th ed., Chapter 13: COPI and COPII Vesicle Coats.

View Details