How Does Your Golgi Go?
Science is shedding new light on the functioning of the cell’s protein processing complex.
Scientists have long sought a robust picture of how the Golgi complex, an organelle critical to the post-translational modification and sorting of newly synthesized proteins, operates. The Golgi contains multiple subcompartments—cis (early), medial (middle) and trans (late) cisternae—each housing different sets of glycosyltransferases and other enzymes. Proteins enter the Golgi at the cis compartment and exit at the trans compartment, but how they move from one cisterna to the next is still somewhat mysterious.
Now, recent findings are helping to resolve the issue.
One model for membrane traffic within the Golgi apparatus has led the pack.1 According to the cisternal maturation (or progression) model, cargo remains in a given compartment and different enzymes arrive there, to convert a cis cisterna into a...
Researchers have directly observed apparent cisternal maturation in yeast: two groups have detected the “conversion” of one Golgi compartment into another using high-resolution, live-cell video microscopy.3,4 But the mammalian Golgi is a tightly stacked structure, making it harder to imagine how compartment progression might take place.
A recently published study also in yeast yielded important new clues as to how Golgi compartments might mature. Yale researcher Peter Novick (now at University of California, San Diego) and colleagues showed how Golgi-localized Rab GTPases could direct the formation of a late Golgi compartment from an earlier one. Cell biologist Félix Rivera-Molina along with Novick used live-cell video microscopy to see Rab conversion happening in the Golgi.5 They visualized a compartment carrying an early Golgi Rab convert to one containing a late Golgi Rab. They also showed that the later-acting Rab recruited a GTPase activating protein to inactivate the earlier-acting Rab, leading to its removal from that compartment. Their data provide a molecular mechanism for compartment interconversion at the Golgi, reminiscent of maturation in the endocytic pathway.
These data support a new way of thinking about molecular events underlying Golgi transport. As is well established for the endocytic pathway, Rab GTPases would label specific subdomains of the Golgi apparatus, recruiting specific Golgi enzymes that direct the functions of each compartment. Compartments would be defined by their distinct Rab GTPases; Rab guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) would segregate individual Rabs into separate locations within the Golgi that could be further compartmentalized by cytoskeletal motor proteins driving compartment fission. The Rabs and their attendant proteins would order cargo within the Golgi stack.6 Indeed, the proteins that stack the cisternae may use a Rab cascade to achieve their position in the stack. At the trans Golgi, Rabs would also orchestrate the collection of cargoes into distinct transport carriers and delivery to their final destinations.
Validation and clarification of this model will require defining which Rabs build which specific Golgi enzyme subcompartments to organize this polarized cellular factory. Unresolved is the question of how cargo moves through the stack—and the potential importance of transport vesicles in this process.
Suzanne Pfeffer is a professor of biochemistry at Stanford University School of Medicine, and a member of the Faculty of Cell Biology at F1000.
This article is an adaptation of an article published in F1000 Biology Reports, a publication of the Faculty of 1000. F1000 Biology consists of more than 2,000 leading biologists (Faculty Members) who select and review the most important published papers in their respective fields (Faculties). The next two pages describe recent selections from various Faculties.