Molecular details of endoplasmic-reticulum–Golgi biogenesis

The SEC screen of Saccharomyces cerevisiae (a genetic screen that is carried out to isolate temperature-sensitive yeast mutants (known as SEC mutants) that are defective in protein secretion) contributed to deciphering the core components of COPII. The coat complex COPII is composed of the small GTPase SAR1, the heterodimer SEC23–SEC24 and a heterotetramer of two SEC13–SEC31 complexes¹²⁸. The GDP-bound form of SAR1 is recruited to the endoplasmic reticulum (ER) membrane by the ER-membrane-bound molecule SEC12 (see figure), which functions as a guanine-nucleotide-exchange factor (GEF) for SAR1 (Ref. 3). The GTP-bound form of SAR1 then recruits the SEC23–SEC24 complex, and together, they form the membrane-proximal layer of the coat. This molecular complex then recruits the SEC13–SEC31 complex, which forms the membrane-distal layer of the coat. These COPII-coated buds also allow the recruitment of ER–Golgi-intermediate-compartment protein 53 (ERGIC53) and cargo proteins, such as p24 and p50, that are destined for other stages of the secretory pathway, as well as the KDEL ER protein-retention receptor.

Numerous other proteins are then recruited to these ER-exit sites, including the vesicle-docking protein p115, SNARE (soluble-N-ethylmaleimide-sensitive-factor accessory-protein receptor) proteins, the GTPase RAB1, and GBF1 (Golgi-specific brefeldin-A-resistance factor 1), which is a GEF for the small GTPase ADP-ribosylation factor 1 (ARF1)⁷. After ARF1 has been activated, it recruits a large number of effector proteins, including ankyrin, spectrin, tubulin and tubulin-associated proteins, as well as components of COPI, to ER-exit sites. The activity of ARF1 and its partners differentiates the ERGIC from ER-exit sites by creating a different lipid-to-protein membrane composition and by physically segregating the ERGIC from the ER. Treatment of cells with brefeldin A, which prevents ARF1 from binding membranes, inhibits formation of the ERGIC and, consequently, formation of the Golgi¹²⁹. However, ER-exit sites are still present, together with the vesicle-docking protein p115, receptors for cargo proteins and proteins that constitute COPII.

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Subcellular localization of syntaxins (red) in a mammalian cell relative to the various membrane-bound compartments, anterograde and endocytotic/retrograde flow of traffic (green and purple arrows, respectively) and known membrane-transport steps (black). EE, early endosome; ERGIC, ER-Golgi intermediate compartment; Glut4, a glucose transporter molecule; LE, late endosome; RE, recycling endosome, SER, smooth ER; syn, syntaxin; TGN, trans-Golgi network.

Teng et al. Genome Biology 2001 2:reviews3012.1   doi:10.1186/gb-2001-2-11-reviews3012