ARFGAP, cargo, v-SNAREs and p24 proteins bind nascent COPI complex

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Reaction [binding]
Homo sapiens
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Binding and polymerization of the coatomer (the COPI coat) is coordinated with the incorporation of cargo proteins and Golgi-targeting snares, as well as with recruitment of ARFGAP proteins (Letourneur et al, 1994; Nagahama et al,1996; Bremser et al, 1999).
Typical model cargo for COPI-mediated trafficking includes the viral glycoprotein VSV-G and proinsulin as well as the KDEL receptors, which bind and recycle ER-resident proteins and which themselves must be returned to post-ER compartments (Cosson and Letourner, 1994; Ben-Tekaya et al, 2005; Majoul et al, 2001; Orci et al, 1997, Bremser et al, 1999; Presley et al, 1997; reviewed in Beck et al, 2009).
Other protein components of the COPI vesicle include the p24 family of proteins, which serve diverse roles in the early secretory pathway (reviewed in Schuiki and Volchuk, 2012). Oligomeric p24 proteins interact with ADP-bound ARF and components of the COPI coat, contributing to coatomer recruitment and oligomerization (Gommel et al, 2001; Majoul et al, 2001; Bethune et al, 2006; Harter and Wieland, 1998; Langer et al, 2008; Reinhard et al, 1999). The p24 proteins also act as cargo receptors for various proteins destined for packaging in COPI vesicles; these include GPI-anchored transmembrane proteins, WNT ligands and some G-protein coupled receptors (Takida et al, 2008; Bonnon et al, 2010; Luo et al, 2011; Beuchling et al, 2011; Wang and Kazanietz, 2002; reviewed in Schuiki and Volchuk, 2012). Finally, the p24 proteins contribute to COPI coat disassembly by restricting ARF GTPase activity until cargo has been loaded (Goldberg, 2000; Lanoix et al, 2001).
ARFGAPs are recruited to the budding vesicle through direct interaction with active ARF, the cytoplasmic tails of cargo proteins and with components of the COPI coat (Goldberg, 2000; Majoul et al, 2001; Aoe et al, 1997; Kliouchnikov et al, 2009; Luo et al, 2009). Stimulation of ARF GTPase activity is coordinated with cargo recruitment to ensure that only cargo-loaded vesicles are produced (Goldberg, 2000; Luo et al, 2009).
Mammalian cells have 3 ARFGAPs that appear to be involved in COPI-mediated traffic, ARFGAP1,2 and 3 (Frigerio et al, 2007; Liu et al, 2001; Kahn et al, 2008). ARFGAP1 has a ALPS domain that recognizes membrane curvature and that is required for the GTPase stimulating activity of the protein, suggesting a mechanism for coordinating ARF1-mediated GTP hydrolysis with vesicle formation (Bigay et al, 2003; Mesmin et al, 2007). ARFGAP 2 and 3 do not contain this motif, and their activity is dependent upon interaction with coatomer (Weimar et al 2008; Kliouchnikov et al, 2009; Luo et al, 2009).
Finally, there is evidence that components of the ankyin/spectrin skeleton may be incorporated in the nascent COPI vesicle, acting as a bridge between cargo proteins and the dynein-dynactin complex required for their transport to the Golgi (Devarajan et al, 1997; Godi et al, 1998; Holleran et al, 1996; Holleran et al, 2001).

Literature References
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Proc. Natl. Acad. Sci. U.S.A. 1997
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Cell 1994
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Letourneur, F, Cosson, P

Science 1994
19015319 Differential roles of ArfGAP1, ArfGAP2, and ArfGAP3 in COPI trafficking

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Cell 1999
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Presley, JF, Lippincott-Schwartz, J, Hirschberg, K, Cole, NB, Zaal, KJ, Schroer, TA

Nature 1997
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Harter, C, Wieland, FT

Proc. Natl. Acad. Sci. U.S.A. 1998
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Morrow, JS, Stankewich, MC, Ligon, LA, Tokito, M, Holzbaur, EL, Holleran, EA

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Hauri, HP, Ben-Tekaya, H, Pepperkok, R, Miura, K

J. Cell. Sci. 2005
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Schuiki, I, Volchuk, A

Biomol Concepts 2012
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Goldberg, J

Cell 2000
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FEBS Lett. 2001
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Biochemistry 2007
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Hell, SW, Straub, M, Majoul, I, Söling, HD, Duden, R

Dev. Cell 2001
14654841 Lipid packing sensed by ArfGAP1 couples COPI coat disassembly to membrane bilayer curvature

Gounon, P, Antonny, B, Bigay, J, Robineau, S

Nature 2003
17760859 Two human ARFGAPs associated with COP-I-coated vesicles

Frigerio, G, Majoul, I, Grimsey, N, Dale, M, Duden, R

Traffic 2007
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Biochem. J. 2008
16940185 Coatomer, the coat protein of COPI transport vesicles, discriminates endoplasmic reticulum residents from p24 proteins

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Mol. Cell. Biol. 2006
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Proc. Natl. Acad. Sci. U.S.A. 1999
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EMBO Rep. 2011
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Traffic 2008
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Cell 1997
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Mol. Biol. Cell 2009
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