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#COPII

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.

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Protein Sorting and Trafficking

What signal is required for COPII-mediated ER-to-Golgi transport?

Selective inclusion of membrane cargo into COPII vesicles instead of bulk flow relies on export signals recognized directly by Sec24 adaptor subunit. Well-characterized ER export code is di-acidic DXE motif positioned four to ten residues downstream of transmembrane domain in cytosolic C-terminal tails of many type I proteins like VSV-G, Sys1, ERGIC-53, SNAREs Bet1, Sec22. Motif consists of Asp-X-Glu where both acidic side chains fit basic pockets formed by arginine and lysine in Sec24 B-site; upstream hydrophobic aromatic residues strengthen interaction. Crystal structures show Sec24C and Sec24D isoforms especially adept binding DXE while Sec24A-B prefer IxM signals. Mutation of DXE to AXA drastically lowers affinity slowing ER exit five to ten fold causing ER retention and degradation. KKXX at extreme C-terminus binds alpha beta prime COP I subunits for Golgi-to-ER retrieval opposite direction. Tyrosine-based YXXPhi recognized by mu subunit of AP complexes for clathrin-mediated TGN to endosome and plasma membrane endocytosis, NPXY recognized by PTB domains of Dab2 and ARH for LDL receptor uptake. Thus DXE uniquely encodes ER exit into COPII for anterograde traffic ensuring efficient export.

Ref: Lodish et al., MCB: DXE di-acidic motif recognized by Sec24 for COPII ER exit.

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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.

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