The Golgi apparatus (GA) is the main station along the secretory pathway. Mechanisms of intra-Golgi transport remain unresolved. Three models compete with each other for the right to be defined as the paradigm. The vesicular model cannot explain the following: (1) lipid droplets and aggregates of procollagen that are larger than coatomer I (COPI)-dependent vesicles are transported across the GA; and (2) most anterograde cargoes are depleted in COPI vesicles. The compartment progression/maturation model has the following problems: (1) most Golgi-resident proteins are depleted in COPI vesicles; (2) there are no COPI vesicles for the recycling of the resident proteins in the trans-most-Golgi cisterna; and (3) different proteins have different rates of intra-Golgi transport. The diffusion model based on permanent inter-cisternal connections cannot explain the existence of lipid, ionic and protein gradients across the Golgi stacks. In contrast, the kiss-and-run model has the potential to explain most of the experimental observations. The kiss-and-run model can be symmetric when fusion and then fission occurs in the same place, and asymmetric when fusion takes place in one location, whereas fission takes place in another. The asymmetric kiss-and-run model resembles the carrier maturation mechanism, and it can be used to explain the transport of large cargo aggregates.
References
[1]
Glick, B.S.; Luini, A. Models for Golgi traffic: A critical assessment. Cold Spring Harb. Perspect. Biol 2011, 3, doi:10.1101/cshperspect.a005215.
[2]
Mironov, A.A.; Beznoussenko, G.V.; Polishchuk, R.S.; Trucco, A. Intra-Golgi transport. A way to a new paradigm? BBA Mol. Cell Res 2005, 1744, 340–350.
[3]
Mironov, A.A.; Beznoussenko, G.V. Intra-Golgi Transport. In The Golgi Apparatus. State of the Art 110 Years after Camillo Golgi’s Discovery; Mironov, A.A., Pavelka, M., Eds.; Springer-Verlag: Berlin, Germany, 2008; pp. 342–357.
[4]
Nakano, A.; Luini, A. Passage through the Golgi. Curr. Opin. Cell Biol 2010, 22, 471–478.
Gilchrist, A.; Au, C.E.; Hiding, J.; Bell, A.W.; Fernandez-Rodriguez, J.; Lesimple, S.; Nagaya, H.; Roy, L.; Gosline, S.J.; Hallett, M.; et al. Quantitative proteomics analysis of the secretory pathway. Cell 2006, 127, 1265–1281.
[7]
Bonfanti, L.; Mironov, A.A., Jr; Martínez-Menárguez, J.A.; Martella, O.; Fusella, A.; Baldassarre, M.; Buccione, R.; Geuze, H.J.; Mironov, A.A.; Luini, A. Procollagen traverses the Golgi stack without leaving the lumen of cisternae: Evidence for cisternal maturation. Cell 1998, 95, 993–1003.
[8]
Orci, L.; Stamnes, M.; Ravazzola, M.; Amherdt, M.; Perrelet, A.; Sollner, T.H.; Rothman, J.E. Bidirectional transport by distinct populations of COPI-coated vesicles. Cell 1997, 90, 335–349.
[9]
Glick, B.S.; Iston, E.T.; Oster, G. A cisternal maturation mechanism can explain the asymmetry of the Golgi stack. FEBS Lett 1997, 414, 177–181.
[10]
Martinez-Menarguez, J.A.; Prekeris, R.; Oorschot, V.M.; Scheller, R.; Slot, J.W.; Geuze, H.J.; Klumperman, J. Peri-Golgi vesicles contain retrograde but not anterograde proteins consistent with the cisternal progression model of intra-Golgi transport. J. Cell Biol 2001, 155, 1213–1224.
[11]
Cosson, P.; Amherdt, M.; Rothman, J.E.; Orci, L. A resident Golgi protein is excluded from peri-Golgi vesicles in NRK cells. Proc. Natl. Acad. Sci. USA 2002, 99, 12831–12834.
[12]
Kweon, H.S.; Beznoussenko, G.V.; Micaroni, M.; Polishchuk, R.S.; Trucco, A.; Martella, O.; di Giandomenico, D.; Marra, P.; Fusella, A.; di Pentima, A.; et al. Golgi enzymes are enriched in perforated zones of Golgi cisternae but are depleted in COPI vesicles. Mol. Biol. Cell 2004, 15, 4710–4724.
[13]
Lucocq, J.; Berger, E.; Hug, C. The pathway of Golgi cluster formation in okadaic acid-treated cells. J. Struct. Biol 1995, 115, 318–330.
[14]
Orci, L.; Amherdt, M.; Ravazzola, M.; Perrelet, A.; Rothman, J.E. Exclusion of Golgi residents from transport vesicles budding from Golgi cisternae in intact cells. J. Cell Biol 2000, 150, 1263–1270.
[15]
Fusella, A.; Micaroni, M.; Di Giandomenico, D.; Mironov, A.A.; Beznoussenko, G.V. COPI vesicles inhibit intra-Golgi transport by sequestration of Qb-SNAREs from Golgi cisternae. Traffic 2012. submitted for publication.
[16]
Berger, E.G.; Hesford, F.J. Localization of galactosyl- and sialyltransferase by immunofluorescence: Evidence for different sites. Proc. Natl. Acad. Sci. USA 1985, 82, 4736–4739.
Rabouille, C.; Hui, N.; Hunte, F.; Kieckbusch, R.; Berger, E.G.; Warren, G.; Nilsson, T. Mapping the distribution of Golgi enzymes involved in the construction of complex oligosaccharides. J. Cell Sci 1995, 108, 1617–1627.
[19]
Ladinsky, M.S.; Mastronarde, D.N.; McIntosh, J.R.; Howell, K.E.; Staehelin, L.A. Golgi structure in three dimensions: Functional insights from the normal rat kidney cell. J. Cell Biol 1999, 144, 1135–1149.
[20]
Ladinsky, M.S.; Wu, C.C.; McIntosh, S.; McIntosh, J.R.; Howell, K. Structure of the Golgi and distribution of reporter molecules at 20 °C reveals the complexity of the exit compartments. Mol. Biol. Cell 2002, 13, 2810–2825.
[21]
Orci, L.; Perrelet, A.; Rothman, J.E. Vesicles on strings: Morphological evidence for processive transport within the Golgi stack. Proc. Natl. Acad. Sci. USA 1998, 95, 2279–2283.
[22]
Luby-Phelps, K. Physical properties of cytoplasm. Curr. Opin. Cell Biol 1994, 6, 3–9.
[23]
Bannykh, S.I.; Plutner, H.; Matteson, J.; Balch, W.E. The role of ARF1 and rab GTPases in polarization of the Golgi stack. Traffic 2005, 6, 803–819.
[24]
Letourneur, F.; Gaynor, E.C.; Hennecke, S.; Démollière, C.; Duden, R.; Emr, S.D.; Riezman, H.; Cosson, P. Coatomer is essential for retrieval of dilysine-tagged proteins to the endoplasmic reticulum. Cell 1994, 79, 1199–1207.
[25]
Matsuura-Tokita, K.; Takeuchi, M.; Ichihara, A.; Mikuriya, K.; Nakano, A. Live imaging of yeast Golgi cisternal maturation. Nature 2006, 441, 1007–1010.
[26]
Oprins, A.; Rabouille, C.; Posthuma, G.; Klumperman, J.; Geuze, H.J.; Slot, J.W. The ER to Golgi interface is the major concentration site of secretory proteins in the exocrine pancreatic cell. Traffic 2001, 2, 831–838.
[27]
Mironov, A.A.; Arvan, P. Origin of the Regulated Secretory Pathway. In The Golgi Apparatus: State of the Art 110 Years after Camillo Golgi’s Discovery; Mironov, A.A., Pavelka, M., Eds.; Springer-Verlag: Berlin, Germany, 2008; pp. 482–515.
[28]
Trucco, A.; Polishchuk, R.S.; Martella, O.; Di Pentima, A.; Fusella, A.; di Giandomenico, D.; San Pietro, E.; Beznoussenko, G.V.; Polishchuk, E.V.; Baldassarre, M.; et al. Secretory traffic triggers the formation of tubular continuities across Golgi sub-compartments. Nat. Cell Biol 2004, 6, 1071–1081.
[29]
Beznoussenko, G.V.; Seetharaman Parashuraman, S.; Polishchuk, R.; Martella, O.; di Giandomenico, D.; Fusella, A.; Spaar, A.; Sallese, M.; Capestrano, M.G.; Pavelka, M.; et al. Secretion of soluble proteins by diffusion via inter-cisternal continuities: A novel intra-Golgi transport mechanism. Nat. Cell Biol 2012. submitted for publication.
[30]
Marra, P.; Salvatore, L.; Mironov, A., Jr; di Campli, A.; di Tullio, G.; Trucco, A.; Beznoussenko, G.; Mironov, A.; de Matteis, M.A. The biogenesis of the Golgi ribbon: The roles of membrane input from the ER and of GM130. Mol. Biol. Cell 2007, 18, 1595–1608.
[31]
Kondylis, V.; Spoorendonk, K.M.; Rabouille, C. dGRASP localization and function in the early exocytic pathway in Drosophila S2 cells. Mol. Biol. Cell 2005, 16, 4061–4072.
[32]
Marsh, B.J.; Volkmann, N.; McIntosh, J.R.; Howell, K.E. Direct continuities between cisternae at different levels of the Golgi complex in glucose-stimulated mouse islet beta cells. Proc. Natl. Acad. Sci. USA 2004, 101, 5565–5570.
[33]
Beznoussenko, G.V.; Scanu, T.; Parashuraman, S.; di Giandomenico, D.; Deerink, T.J.; Martone, M.E.; Vos, M.R.; Rikers, Y.G.M.; Mironov, A.A. In situ, COPII and COPI vesicles are depleted of anterograde and retrograde cargo correspondingly. Mol. Cell Biol 2012. to be submitted for publication.
[34]
Bouchet-Marquis, C.; Starkuviene, V.; Grabenbauer, M. Golgi apparatus studied in vitreous sections. J. Microsc 2008, 230, 308–316.
[35]
Patterson, G.H.; Hirschberg, K.; Polishchuk, R.S.; Gerlich, D.; Phair, R.D.; Lippincott-Schwartz, J. Transport through the Golgi apparatus by rapid partitioning within a two-phase membrane system. Cell 2008, 133, 1055–1067.
[36]
Pagano, R.E.; Sepanski, M.A.; Martin, O.C. Molecular trapping of a fluorescent ceramide analogue at the Golgi apparatus of fixed cells: Interaction with endogenous lipids provides a trans-Golgi marker for both light and electron microscopy. J. Cell Biol 1989, 109, 2067–2079.
[37]
Mironov, A.A.; Colanzi, A.; Polishchuk, R.S.; Beznoussenko, G.V.; Mironov, A.A., Jr; Fusella, A.; di Tullio, G.; Silletta, M.G.; Corda, D.; de Matteis, M.A.; Luini, A. Dicumarol, an inhibitor of ADP-ribosylation of CtBP3/BARS, fragments Golgi non-compact tubular zones and inhibits intra-Golgi transport. Eur. J. Cell Biol. 2004, 83, 263–279.
[38]
Mavillard, F.; Hidalgo, J.; Megias, D.; Levitsky, K.L.; Velasco, A. PKA-mediated Golgi remodeling during cAMP signal transmission. Traffic 2010, 11, 90–109.
[39]
Pagano, R.E.; Longmuir, K.J. Phosphorylation, transbilayer movement, and facilitated intracellular transport of diacylglycerol are involved in the uptake of a fluorescent analog of phosphatidic acid by cultured fibroblasts. J. Biol. Chem 1985, 260, 1909–1916.
[40]
Sleight, R.G.; Pagano, R.E. Rapid appearance of newly synthesized phosphatidylethanolamine at the plasma membrane. J. Biol. Chem 1983, 258, 9050–9058.
[41]
Stinchcombe, J.C.; Nomoto, H.; Cutler, D.F.; Hopkins, C.R. Anterograde and retrograde traffic between the rough endoplasmic reticulum and the Golgi complex. J. Cell Biol 1995, 131, 1387–1401.
[42]
Hermo, L.; Smith, C.E. The structure of the Golgi apparatus: A sperm’s eye view in principal epithelial cells of the rat epididymis. Histochem. Cell Biol 1998, 109, 431–447.
[43]
Rambourg, A.; Clermont, Y. Three-Dimensional Structure of the Golgi Apparatus in Mammalian Cells. In The Golgi Apparatus; Roth, J., Berger, E.G., Eds.; Birkhauser: Basel, Switzerland, 1997; pp. 37–61.
[44]
Krijnse-Locker, J.; Ericsson, M.; Rottier, P.J.; Griffiths, G. Characterization of the budding compartment of mouse hepatitis virus: Evidence that transport from the RER to the Golgi complex requires only one vesicular transport step. J. Cell Biol 1994, 124, 55–70.
[45]
Ladinsky, M.S.; Kremer, J.R.; Furcinitti, P.S.; McIntosh, J.R.; Howell, K.E. HVEM tomography of the trans-Golgi network: Structural insights and identification of a lace-like vesicle coat. J. Cell Biol 1994, 127, 29–38.
[46]
Clermont, Y.; Rambourg, A.; Hermo, L. Connections between the various elements of the cis- and mid-compartments of the Golgi apparatus of early rat spermatids. Anat. Rec 1994, 240, 469–480.
[47]
Griffiths, G.; Pepperkok, R.; Locker, J.K.; Kreis, T.E. Immunocytochemical localization of beta-COP to the ER-Golgi boundary and the TGN. J. Cell Sci 1995, 108, 2839–2856.
[48]
Griffiths, G.; Ericsson, M.; Krijnse-Locker, J.; Nilsson, T.; Goud, B.; S?ling, H.D.; Tang, B.L.; Wong, S.H.; Hong, W. Localization of the Lys, Asp, Glu, Leu tetrapeptide receptor to the Golgi complex and the intermediate compartment in mammalian cells. J. Cell Biol 1994, 127, 1557–1574.
[49]
Mironov, A.A.; Weidman, P.; Luini, A. Variations on the intracellular transport theme: Maturing cisternae and trafficking tubules. J. Cell Biol 1997, 138, 481–484.
[50]
Tanaka, K.; Mitsushima, A.; Fukudome, H.; Kashima, Y. Three-dimensional architecture of the Golgi complex observed by high resolution scanning electron microscopy. J. Submicrosc. Cytol 1986, 18, 1–9.
[51]
Cluett, E.B.; Kuismanen, E.; Machamer, C.E. Heterogeneous distribution of the unusual phospholipid semilysobisphosphatidic acid through the Golgi complex. Mol. Biol. Cell 1997, 8, 2233–2240.
[52]
Orci, L.; Montesano, R.; Meda, P.; Malaisse-Lagae, F.; Brown, D.; Perrelet, A.; Vassalli, P. Heterogeneous distribution of filipin-cholesterol complexes across the cisternae of the Golgi apparatus. Proc. Natl. Acad. Sci. USA 1981, 78, 293–297.
[53]
Mironov, A.A.; Beznoussenko, G.V.; Nicoziani, P.; Martella, O.; Trucco, A.; Kweon, H.S.; di Giandomenico, D.; Polishchuk, R.S.; Fusella, A.; Lupetti, P.; et al. Small cargo proteins and large aggregates can traverse the Golgi by a common mechanism without leaving the lumen of cisternae. J. Cell Biol 2001, 155, 1225–1238.
[54]
Volchuk, A.; Amherdt, M.; Ravazzola, M.; Brügger, B.; Rivera, V.M.; Clackson, T.; Perrelet, A.; S?llner, T.H.; Rothman, J.E.; Orci, L. Megavesicles implicated in the rapid transport of intracisternal aggregates across the Golgi stack. Cell 2000, 102, 335–348.
[55]
Perinetti, G.; Müller, T.; Spaar, A.; Polishchuk, R.; Luini, A.; Egner, A. Correlation of 4Pi- and electron microscopy to study transport through single Golgi stacks in living cells with super resolution. Traffic 2009, 10, 379–391.
[56]
Ceccarelli, B.; Hurlbut, W.P.; Mauro, A. Depletion of vesicles from frog neuromuscular junctions by prolonged tetanic stimulation. J. Cell Biol 1972, 54, 30–38.
[57]
Roberts, R.L.; Barbieri, M.A.; Pryse, K.M.; Chua, M.; Morisaki, J.H.; Stahl, P.D. Endosome fusion in living cells overexpressing GFP-rab5. J. Cell Sci. 1999, 112, 3667–3675.
[58]
Van Kempen, G.T.; van der Leest, H.T.; van den Berg, R.J.; Eilers, P.; Westerink, R.H. Three distinct modes of exocytosis revealed by amperometry in neuroendocrine cells. Biophys. J 2011, 100, 968–977.
[59]
Jaiswal, J.K.; Rivera, V.M.; Simon, S.M. Exocytosis of post-Golgi vesicles is regulated by components of the endocytic machinery. Cell 2009, 137, 1308–1319.
Quinn, P.; Griffiths, G.; Warren, G. Density of newly synthesized plasma membrane proteins in intracellular membranes II. Biochemical studies. J. Cell Biol 1984, 98, 2142–2147.
[62]
Beznoussenko, G.V.; Fusella, A.; Ragnini, A.; Ellinger, A.; Wilson, C.; Mironov, A.A. Three-dimensional structure of the Golgi in yeast S. cerevisiae and mechanisms of intracellular transport. Traffic 2012. to be submitted for publication.
[63]
Micaroni, M.; Perinetti, G.; Di Giandomenico, D.; Bianchi, K.; Spaar, A.; Mironov, A.A. Synchronous intra-Golgi transport induces the release of Ca2+ from the Golgi apparatus. Exp. Cell Res 2010, 316, 2071–2086.
[64]
Beznoussenko, G.V.; Vetterlein, M.; Neumuller, J.; Giandomenico, D.; Bao Cutrona, M.; Ellinger, A.; Pavelka, M.; Mironov, A.A. In the transporting Golgi stacks, Golgin-97 facilitates the attachment of the trans-most cisternae to the last medial cisterna. Nat. Cell Biol 2012. to be submitted for publication.
[65]
Weidman, P.; Roth, R.; Heuser, J. Golgi membrane dynamics imaged by freeze-etch electron microscopy: Views of different membrane coatings involved in tubulation versus vesiculation. Cell 1993, 75, 123–133.
[66]
Yang, J.S.; Lee, S.Y.; Spanò, S.; Gad, H.; Zhang, L.; Nie, Z.; Bonazzi, M.; Corda, D.; Luini, A.; Hsu, V.W. A role for BARS at the fission step of COPI vesicle formation from Golgi membrane. EMBO J 2005, 24, 4133–4143.
[67]
Yang, J.S.; Zhang, L.; Lee, S.Y.; Luini, A.; Hsu, V.W. Key components of the fission machinery are interchangeable. Nat. Cell Biol 2006, 8, 1376–1382.
[68]
Weinstock, M.; Leblond, C.P. Synthesis, migration, and release of precursor collagen by odontoblasts as visualized by radioautography after (3H)proline administration. J. Cell Biol 1974, 60, 92–127.
[69]
Bergmann, J.E. Using temperature-sensitive mutants of VSV to study membrane protein biogenesis. Methods Cell Biol 1989, 32, 85–110.
[70]
Griffiths, G. Gut thoughts on the Golgi complex. Traffic 2000, 1, 738–745.
[71]
Bergmann, J.E.; Tokuyasu, K.T.; Singer, S.J. Passage of an integral membrane protein, the vesicular stomatitis virus glycoprotein, through the Golgi apparatus en route to the plasma membrane. Proc. Natl. Acad. Sci. USA 1981, 78, 1746–1750.
[72]
Rothman, J.E.; Bursztyn-Pettegrew, H.; Fine, R.E. Transport of the membrane glycoprotein of vesicular stomatitis virus to the cell surface in two stages by clathrin-coated vesicles. J. Cell Biol 1980, 86, 162–171.
[73]
Bannykh, S.; Aridor, M.; Plutner, H.; Rowe, T.; Balch, W.E. Regulated export of cargo from the endoplasmic reticulum of mammalian cells. Cold Spring Harb. Symp. Quant. Biol 1995, 60, 127–137.
[74]
Orci, L.; Ravazzola, M.; Volchuk, A.; Engel, T.; Gmachl, M.; Amherdt, M.; Perrelet, A.; Sollner, T.H.; Rothman, J.E. Anterograde flow of cargo across the golgi stack potentially mediated via bidirectional “percolating” COPI vesicles. Proc. Natl. Acad. Sci. USA 2000, 97, 10400–10405.
[75]
Huang, C.; Chang, A. pH-dependent cargo sorting from the Golgi. J. Biol. Chem 2011, 286, 10058–10065.
[76]
Beznoussenko, G.V.; Mironov, A.A. Models of intracellular transport and evolution of the Golgi complex. Anat. Rec 2002, 268, 226–238.
[77]
Mironov, A.A.; Luini, A.; Buccione, R. Constitutive transport between the trans-Golgi network and the plasma membrane according to the maturation model. A hypothesis. FEBS Lett 1998, 440, 99–102.
[78]
Mironov, A., Jr; Luini, A.; Mironov, A. A synthetic model of intra-Golgi traffic. FASEB J. 1998, 12, 249–252.