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The ER–Golgi Membrane System: Compartmental Organization and Protein Traffic

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Abstract

The sections in this article are:

1 Organization of the ER‐Golgi Membrane System
1.1 Endoplasmic Reticulum
1.2 Golgi Apparatus
1.3 ER‐Golgi Intermediate Compartment
2 Anterograde (Exocytotic) Protein Traffic From ER to Golgi
2.1 Acquisition of Transport Competence in the ER
2.2 COPI‐ and COPII‐Coated Transport Vesicles
2.3 Vesicle Docking and Fusion
2.4 GTPases
2.5 Role of the ERGIC in ER‐to‐Golgi Transport
3 Protein Retention and Retrieval
3.1 Membrane Flow, Selective Transport, and Protein Retention
3.2 Soluble ER proteins
3.3 ER and ERGIC Membrane Proteins
3.4 Golgi Membrane Proteins
4 Retrograde Protein Traffic
4.1 Insights from Brefeldin A
4.2 Recycling from the cis‐Golgi
4.3 Role of the ERGIC and Possible Role of ERGIC‐53
5 Regulation of Membrane Traffic in the Early Secretory Pathway and Maintenance of Organelle Structure
6 Conclusions and Prospects
Figure 1. Figure 1.

Structural and functional compartmentalization of the early secretory pathway of mammalian cells. ER, endoplasmic reticulum; TE, transitional element of the rough ER. Note: Unlike as is depicted in this scheme, the ER‐Golgi intermediate compartment consists of a multitude of tubulovesicular membrane clusters, some of which are not localized near the Golgi apparatus.

Figure 2. Figure 2.

Alternative Golgi models. A. In the minimal compartment model 294 the Golgi apparatus is believed to consist of three compartments. Secretory proteins traverse the Golgi apparatus from cis to trans in two vesicular steps (arrows). B. In the five‐compartment model 416 the central Golgi stack is further subdivided into three additional compartments named cis, medial, and trans. Transit through the Golgi requires four vesicular steps (arrows). C. In the maturation model 258,307,428 the cis‐Golgi network (CGN) cisterna gradually matures to the trans‐Golgi network (TGN) (indicated by dotted arrow) and hence anterograde protein transport through the Golgi would not require the formation of vesicles. Compartmentalization of Golgi enzymes would be maintained by their recycling to earlier cisternae (arrows) either by vesicular or tubular transport.

Figure 3. Figure 3.

Appearance of the ER‐Golgi intermediate compartment (ERGIC) in ultrathin cryosections in enterocytes of a human small intestinal biopsy sample

Courtesy of J.A.M Fransen). The ERGIC was labeled with a mouse mAb against ERGIC‐53 followed by incubations with rabbit‐anti‐mouse and 5 nm colloidal gold‐protein A. The ERGIC consists of tubulovesicular membrane clusters (circled). G, Golgi apparatus, N, nucleus
Figure 4. Figure 4.

Models for budding and targeting of transport vesicles in the early secretory pathway illustrating similarities between COPI‐mediated transport (A) and COPII‐mediated transport (B). Precisely which pathways depend on the two different coat complexes is currently debated. A speculative view is that COPI‐mediated transport (mainly established in a mammalian in vitro system) 414 operates in anterograde direction between ERGIC and cis‐Golgi as well as in retrograde direction from cis‐Golgi and ERGIC back to the ER. COPII vesicles (mainly established for yeast) 28,434 may mediate anterograde transport between ER and ERGIC. The v‐SNAREs and t‐SNAREs of the COPI dependent pathway(s) have not been identified. V‐SNARE/t‐SNARE interactions may be multimeric.

Figure 5. Figure 5.

Transport inhibitors for anterograde and retrograde transport in the early secretory pathway of mammalian cells in vivo as deduced from morphological and subcellular fractionation experiments 196,270,383,442. dog, deoxy‐glucose.



Figure 1.

Structural and functional compartmentalization of the early secretory pathway of mammalian cells. ER, endoplasmic reticulum; TE, transitional element of the rough ER. Note: Unlike as is depicted in this scheme, the ER‐Golgi intermediate compartment consists of a multitude of tubulovesicular membrane clusters, some of which are not localized near the Golgi apparatus.



Figure 2.

Alternative Golgi models. A. In the minimal compartment model 294 the Golgi apparatus is believed to consist of three compartments. Secretory proteins traverse the Golgi apparatus from cis to trans in two vesicular steps (arrows). B. In the five‐compartment model 416 the central Golgi stack is further subdivided into three additional compartments named cis, medial, and trans. Transit through the Golgi requires four vesicular steps (arrows). C. In the maturation model 258,307,428 the cis‐Golgi network (CGN) cisterna gradually matures to the trans‐Golgi network (TGN) (indicated by dotted arrow) and hence anterograde protein transport through the Golgi would not require the formation of vesicles. Compartmentalization of Golgi enzymes would be maintained by their recycling to earlier cisternae (arrows) either by vesicular or tubular transport.



Figure 3.

Appearance of the ER‐Golgi intermediate compartment (ERGIC) in ultrathin cryosections in enterocytes of a human small intestinal biopsy sample

Courtesy of J.A.M Fransen). The ERGIC was labeled with a mouse mAb against ERGIC‐53 followed by incubations with rabbit‐anti‐mouse and 5 nm colloidal gold‐protein A. The ERGIC consists of tubulovesicular membrane clusters (circled). G, Golgi apparatus, N, nucleus


Figure 4.

Models for budding and targeting of transport vesicles in the early secretory pathway illustrating similarities between COPI‐mediated transport (A) and COPII‐mediated transport (B). Precisely which pathways depend on the two different coat complexes is currently debated. A speculative view is that COPI‐mediated transport (mainly established in a mammalian in vitro system) 414 operates in anterograde direction between ERGIC and cis‐Golgi as well as in retrograde direction from cis‐Golgi and ERGIC back to the ER. COPII vesicles (mainly established for yeast) 28,434 may mediate anterograde transport between ER and ERGIC. The v‐SNAREs and t‐SNAREs of the COPI dependent pathway(s) have not been identified. V‐SNARE/t‐SNARE interactions may be multimeric.



Figure 5.

Transport inhibitors for anterograde and retrograde transport in the early secretory pathway of mammalian cells in vivo as deduced from morphological and subcellular fractionation experiments 196,270,383,442. dog, deoxy‐glucose.

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Hans‐Peter Hauri, Anja Schweizer. The ER–Golgi Membrane System: Compartmental Organization and Protein Traffic. Compr Physiol 2011, Supplement 31: Handbook of Physiology, Cell Physiology: 605-647. First published in print 1997. doi: 10.1002/cphy.cp140115