#retrograde transport

Protein Sorting and Trafficking

Which protein mediates retrograde transport of ER proteins from the Golgi?

Maintaining ER proteome against continuous leakage via bulk flow into Golgi relies active retrieval preventing depletion resident chaperones folding enzymes. ER membrane proteins expose C-terminal dilysine motif KKXX or KXKXX with two lysines at -3 -4 positions relative extreme C-terminus recognized directly WD40 beta-propeller domains COPI subunits alpha-COP beta prime-COP binding dilysine pH independent. Soluble ER luminal residents like BiP HSPA5 GRP94 PDI calreticulin bear C-terminal KDEL; after escape bind KDEL receptor family Erd2 homologs KDELR1-3 seven transmembrane proteins concentrat

Ref: Bethune et al., Cold Spring Harb Perspect Biol 2006: COPI retrieval of ER proteins from Golgi.

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

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

View Details

Protein Sorting and Trafficking

How does the KDEL receptor regulate protein retrieval?

ER lumen contains chaperones BiP HSPA5, Grp94 HSP90B1, PDI family, calreticulin that may leak into Golgi during non-selective bulk flow; retention therefore relies on active retrieval not static retention. Soluble residents carry C-terminal KDEL tetrapeptide Lys-Asp-Glu-Leu or variant HDEL. If they escape to cis-Golgi beyond, KDEL receptors family of seven-transmembrane proteins Erd2 in yeast KDELR1-3 in mammals concentrated in Golgi and ERGIC recognize tetrapeptide. Binding strongly pH dependent because histidine residues protonate at mildly acidic Golgi lumen pH 6.0-6.2 stabilizing interacti

Ref: Alberts et al., MBC Chapter 13: KDEL receptor pH-dependent retrieval to ER via COPI.

View Details

Protein Sorting and Trafficking

In the vesicle transport model, how are Golgi-resident proteins returned to their compartments?

Golgi organization is explained by cisternal maturation model where new cis cisternae arise from fusion of ER-derived COPII vesicles at ERGIC and progressively mature into trans cisternae carrying secretory cargo forward toward trans-Golgi network. Resident processing enzymes, including cis mannosidases, medial GlcNAc transferases and trans sialyltransferases, cannot move forward with cargo otherwise compartmental polarity would be lost and glycosylation random. To preserve sequential enzyme gradients, transmembrane residents are selectively extracted into COPI-coated vesicles that transport r

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 13: Cisternal maturation and COPI retrograde Golgi traffic.

View Details