Saturday, 20 July 2013 20:00

Final Nail in the Golgi Vesicular Transport Coffin?

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GolgiGolgi "pita pocket" stacks in cross-section
surrounded by Golgi vesicles
Photo credit: The Cell Image Library
For nearly 30 years, cell biologists have investigated—and argued about—how proteins move through an organelle that resembles stacks of pita bread, the Golgi apparatus. The Golgi, named for its discoverer, the great Italian microscopist, Camillo Golgi, is a series of protein processing and sorting compartments in which the pita pockets are called Golgi cisternae. The apparatus though works less like a bakery and more like a series of factory buildings where important accessories are added to proteins. Inside each factory building, specialized workers (enzymes) add different modifications and sort the cargo (proteins).

The Golgi has been thoroughly studied, and defects in the Golgi have been linked to muscular dystrophy. Golgi problems can also contribute to diabetes, cancer, and cystic fibrosis, so researchers have been keen to find treatments to keep the factory going. And yet, until recently, it has been unclear whether new Golgi cargo is housed in one building with the factory workers traveling between buildings to add modifications (the cisternal maturation hypothesis) or whether the factory workers stay in the same building while the cargo moves between buildings (the vesicular transport hypothesis). Now, thanks to Ricardo Rizzo at the Institute of Protein Biochemistry in Naples, Italy, and colleagues, we may have the definitive answer. The vesicular transport hypothesis may be pita toast.

Early electron microscopy suggested that Golgi resident enzymes were distributed asymmetrically through Golgi stacks. Scientists hypothesized that Golgi vesicles delivered cargo sequentially forward to each Golgi cisternae, which is the vesicular transport hypothesis. However, large proteins like procollagen can't be packaged into small vesicles and researchers had observed Golgi enzymes in small COPI vesicles between cisternae. These scientists proposed the cisternal maturation hypothesis in which Golgi enzymes traffic retrograde through each cargo-containing compartment instead of cargo trafficking between Golgi cisternae. Without clear evidence for one of these models, hybrid models have been proposed, including the kiss-and-run model, cisternal progenitor model, and a two-phase membrane model. Although cisternal maturation has been directly visualized in yeast, the mechanism was still not certain in mammalian cells.

A paper published in June in the Journal of Cell Biology1 drives what may be the final nail into the vesicular transport hypothesis coffin. Rizzo and colleagues devised a clever way to address the Golgi question in mammalian cells. They manipulated a subset of Golgi workers in a way that caused them to become stuck together. The researchers showed that when stuck together, the workers could not leave the factory to travel to other buildings. However, when they added a small molecule to unglue the workers, they quickly travelled to other buildings.

More technically, Rizzo et al added FM domains to α-1,2-mannosidase IB, a cis/medial Golgi enzyme, which caused the protein to spontaneously polymerize and form large protein networks. This polymerization prevented the enzyme from entering COPI vesicles and tubules, but was reversible upon addition of a small molecule. The polymerized enzyme moved forward through the Golgi stacks to the trans-Golgi, but moved backwards after the small molecule was added to reverse the polymerization. This evidence for the retrograde trafficking of a Golgi enzyme supports a Golgi model that includes cisternal maturation. In short, the worker enzymes move, the Golgi cargo waits.

1Rizzo R, Parashuraman S, Mirabelli P, Puri C, Lucocq J, Luini A. (2013). The dynamics of engineered resident proteins in the mammalian Golgi complex relies on cisternal maturation. J Cell Biol. 201(7):1027-1036.

Christina Szalinski

Christina is a science writer for the American Society for Cell Biology. She earned her Ph.D. in Cell Biology and Molecular Physiology at the University of Pittsburgh.

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