Golgi apparatus

Because of its large size and distinctive structure, the Golgi apparatus was one of the first organelles to be discovered and observed in detail. It was discovered in 1898 by Italian physician Camillo Golgi during an investigation of the nervous system. After first observing it under his microscope, he termed the structure as apparato reticolare interno ("internal reticular apparatus"). Some doubted the discovery at first, arguing that the appearance of the structure was merely an optical illusion created by Golgi's observation technique. With the development of modern microscopes in the twentieth century, the discovery was confirmed. Early references to the Golgi apparatus referred to it by various names, including the Golgi–Holmgren apparatus, Golgi–Holmgren ducts, and Golgi–Kopsch apparatus. The term Golgi apparatus was used in 1910 and first appeared in scientific literature in 1913, while "Golgi complex" was introduced in 1956. == Subcellular localization ==

The subcellular localization of the Golgi apparatus varies among eukaryotes. In mammals, a single Golgi apparatus is usually located near the cell nucleus, close to the centrosome. Tubular connections are responsible for linking the stacks together. Localization and tubular connections of the Golgi apparatus are dependent on microtubules. In experiments, it is seen that as microtubules are depolymerized, the Golgi apparatuses lose mutual connections and become individual stacks throughout the cytoplasm. In yeast, multiple Golgi apparatuses are scattered throughout the cytoplasm (as observed in Saccharomyces cerevisiae). In plants, Golgi stacks are not concentrated at the centrosomal region and do not form Golgi ribbons. Organization of the plant Golgi depends on actin cables and not microtubules. == Structure ==

In most eukaryotes, the Golgi apparatus is made up of a series of compartments and is a collection of fused, flattened membrane-enclosed disks known as cisternae (singular: cisterna, also called "dictyosomes"), originating from vesicular clusters that bud off the endoplasmic reticulum (ER). A mammalian cell typically contains 40 to 100 stacks of cisternae. Between four and eight cisternae are usually present in a stack; however, in some protists, as many as sixty cisternae have been observed. There are structural and organizational differences in the Golgi apparatus among eukaryotes. In some yeasts, Golgi stacking is not observed. Pichia pastoris does have stacked Golgi, while Saccharomyces cerevisiae does not. In all eukaryotes, each cisternal stack has a cis entry face and a trans exit face. These faces are characterized by unique morphology and biochemistry. Within individual stacks are assortments of enzymes responsible for selectively modifying protein cargo. These modifications influence the fate of the protein. The compartmentalization of the Golgi apparatus is advantageous for separating enzymes, thereby maintaining consecutive and selective processing steps: enzymes catalyzing early modifications are gathered in the cis face cisternae, and enzymes catalyzing later modifications are found in trans face cisternae of the Golgi stacks. == Function ==

The Golgi apparatus is a major collection and dispatch station of protein products received from the endoplasmic reticulum. Proteins synthesized in the ER are packaged into vesicles, which then fuse with the Golgi apparatus. These cargo proteins are modified and destined for secretion via exocytosis or for use in the cell. In this respect, the Golgi can be thought of as similar to a post office: it packages and labels items which it then sends to different parts of the cell or to the extracellular space. The Golgi apparatus is also involved in lipid transport and lysosome formation. The structure and function of the Golgi apparatus are intimately linked. Individual stacks have different assortments of enzymes, allowing for progressive processing of cargo proteins as they travel from the cisternae to the trans Golgi face. and phosphates (phosphorylation). Protein modifications may form a signal sequence that determines the final destination of the protein. For example, the Golgi apparatus adds a mannose-6-phosphate label to proteins destined for lysosomes. Another important function of the Golgi apparatus is in the formation of proteoglycans. Enzymes in the Golgi append proteins to glycosaminoglycans, thus creating proteoglycans. Glycosaminoglycans are long unbranched polysaccharide molecules present in the extracellular matrix of animals. == Vesicular transport ==

; 2. Nuclear pore; 3. Rough endoplasmic reticulum (RER); 4. Smooth endoplasmic reticulum (SER); 5. Ribosome attached to RER; 6. Macromolecules; 7. Transport vesicles; 8. Golgi apparatus; 9. Cis face of Golgi apparatus; 10. Trans face of Golgi apparatus; 11. Cisternae of the Golgi apparatus. The vesicles that leave the rough endoplasmic reticulum are transported to the cis face of the Golgi apparatus, where they fuse with the Golgi membrane and empty their contents into the lumen. Once inside the lumen, the molecules are modified, then sorted for transport to their next destinations. Those proteins destined for areas of the cell other than either the endoplasmic reticulum or the Golgi apparatus are moved through the Golgi cisternae towards the trans face, to a complex network of membranes and associated vesicles known as the trans-Golgi network (TGN). This area of the Golgi is the point at which proteins are sorted and shipped to their intended destinations by their placement into one of at least three different types of vesicles, depending upon the signal sequence they carry. == Current models of vesicular transport and trafficking ==

Model 1: Anterograde vesicular transport between stable compartments • In this model, the Golgi is viewed as a set of stable compartments that work together. Each compartment has a unique collection of enzymes that work to modify protein cargo. Proteins are delivered from the ER to the cis face using COPII-coated vesicles. Cargo then progress toward the trans face in COPI-coated vesicles. This model proposes that COPI vesicles move in two directions: anterograde vesicles carry secretory proteins, while retrograde vesicles recycle Golgi-specific trafficking proteins. • Strengths: The model explains observations of compartments, polarized distribution of enzymes, and waves of moving vesicles. It also attempts to explain how Golgi-specific enzymes are recycled. • Strengths: This model encompasses the strengths of the cisternal progression/maturation model that also explains rapid trafficking of cargo, and how native Golgi proteins can recycle independently of COPI vesicles. • Weaknesses: This model cannot explain the transport kinetics of large protein cargo, such as collagen. Additionally, tubular connections are not prevalent in plant cells. The roles that these connections have can be attributed to a cell-specific specialization rather than a universal trait. If the membranes are continuous, that suggests the existence of mechanisms that preserve the unique biochemical gradients observed throughout the Golgi apparatus. Model 4: Rapid partitioning in a mixed Golgi • This rapid partitioning model is the most drastic alteration of the traditional vesicular trafficking point of view. Proponents of this model hypothesize that the Golgi works as a single unit, containing domains that function separately in the processing and export of protein cargo. Cargo from the ER move between these two domains, and randomly exit from any level of the Golgi to their final location. This model is supported by the observation that cargo exits the Golgi in a pattern best described by exponential kinetics. The existence of domains is supported by fluorescence microscopy data. • Strengths: Notably, this model explains the exponential kinetics of cargo exit of both large and small proteins, whereas other models cannot. • Weaknesses: This model cannot explain the transport kinetics of large protein cargo, such as collagen. This model falls short on explaining the observation of discrete compartments and polarized biochemistry of the Golgi cisternae. It also does not explain formation and disintegration of the Golgi network, nor the role of COPI vesicles. Model 5: Stable compartments as cisternal model progenitors • This is the most recent model. In this model, the Golgi is seen as a collection of stable compartments defined by Rab (G-protein) GTPases. • Strengths: This model is consistent with numerous observations and encompasses some of the strengths of the cisternal progression/maturation model. Additionally, what is known of the Rab GTPase roles in mammalian endosomes can help predict putative roles within the Golgi. This model is unique in that it can explain the observation of "megavesicle" transport intermediates. • Weaknesses: This model does not explain morphological variations in the Golgi apparatus, nor define a role for COPI vesicles. This model does not apply well for plants, algae, and fungi in which individual Golgi stacks are observed (transfer of domains between stacks is not likely). Additionally, megavesicles are not established to be intra-Golgi transporters. Though there are multiple models that attempt to explain vesicular traffic throughout the Golgi, no individual model can independently explain all observations of the Golgi apparatus. Currently, the cisternal progression/maturation model is the most accepted among scientists, accommodating many observations across eukaryotes. The other models are still important in framing questions and guiding future experimentation. Among the fundamental unanswered questions are the directionality of COPI vesicles and role of Rab GTPases in modulating protein cargo traffic. == Brefeldin A ==

Brefeldin A (BFA) is a fungal metabolite used experimentally to disrupt the secretion pathway as a method of testing Golgi function. BFA blocks the activation of some ADP-ribosylation factors (ARFs). ARFs are small GTPases which regulate vesicular trafficking through the binding of COPs to endosomes and the Golgi. BFA inhibits the function of several guanine nucleotide exchange factors (GEFs) that mediate GTP-binding of ARFs. Treatment of cells with BFA thus disrupts the secretion pathway, promoting disassembly of the Golgi apparatus and distributing Golgi proteins to the endosomes and ER. ==See also==

File:YeastGolgiMovieeLifec.ogg|Yeast Golgi dynamics. Green labels early Golgi, red labels late Golgi. File:GolgiRibbonc.jpg|Two Golgi stacks connected as a ribbon in a mouse cell. Taken from the movie. File:GolgiScyl1c.jpg|Three-dimensional projection of a mammalian Golgi stack imaged by confocal microscopy and volume surface rendered using Imaris software. Taken from the movie. == References ==