Nanomedicine, Volume I: Basic Capabilities
© 1999 Robert A. Freitas Jr. All Rights Reserved.
Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999
18.104.22.168 Golgi Complex
The Golgi complex (GC) is a multicisternal membranous structure crudely similar to the rough ER (minus the ribosomes). Substances synthesized by the ER usually pass via vesicles traversing the cytoplasm on microtubule tracks to the Golgi complex, where they are further processed, concentrated, sorted, containerized in appropriate self-identifying new vesicles, and then shipped out to various destinations. Some oligosaccharides are synthesized in the ER, while extensive portions of the same structures are degraded in the Golgi -- competing sets of reactions that are crucial in fixing the "address" of the intracellular compartment to which a newly synthesized macromolecule will be sent. Thus the GC serves as a production editor, allowing several successive sorting steps to take place while reducing the overall cytomanufacturing error rate. The Golgi acts as a "countercurrent" fractionation system to separate proteins destined for the plasma membrane from those to be retained in the ER.1116
Morphologically, the Golgi complex consists of a series of flattened, membranous saccules (Fig. 8.39), forming disk-shaped cisternae that are stacked together to form a cup-shaped structure. Cisternal boundaries are morphologically distinct and are only rarely, if at all, connected.3439,3440 A series of 5-8 saccules comprises a single Golgi stack or dictyosome, typically measuring ~1 micron in diameter and ~250 nm thick. As with the ER, the size and number of Golgi complexes vary according to cell type and metabolic activity. All eukaryotic cells have a GC. Some cells have just one stack; others, particularly those especially active in secretion, may have hundreds.531 One enzyme, thiamine pyrophosphatase, occurs only in Golgi membranes,939 and galactosyl transferase is found only in the GC.996 These may be used by nanorobots as unique cytochemical markers of the Golgi complex.
The Golgi complex is a dynamic structure. The saccules of the GC form by the fusion of vesicles budded off from the ER. As these vesicles reach the GC and fuse, they give rise to new saccules on the forming ("cis") face of the organelle. Existing saccules move forward (outward) in the stack. Meanwhile, on the maturing ("trans") face of the GC, vesicles bud off the tips of the saccules continuously and exit the complex, transported on cytoskeletal elements through an interaction with motor proteins. This is known as the "cisternal maturation model."2347,3443-3445 Within the Golgi, net membrane flow can be quite rapid. In certain mucus-secreting cells of the intestinal mucosa, it takes only ~2000 sec for membrane components to move from the forming face of a Golgi stack to the maturing face.939 Vesicles exhibiting COPI (coat protein I) apparently transport some proteins backwards, both within the Golgi stack and also from the Golgi to the ER.2347 One study counted ~400 individual vesicles in transit within ~0.2 microns of a ~4 micron3 region containing 2 stacks of 7 cisternae.3440
The two faces of a Golgi stack are biochemically distinct. Specific enzymes and receptor proteins are concentrated in the cisterna on the "cis" face of the stack (the "receiving" end), while other proteins are localized mainly in the cisterna on the "trans" face (the "shipping" end). For example, the receptor protein for the carbohydrate mannose-6-phosphate (M6P) is present only in the forming cisterna of the Golgi stack, thus allowing the stack to recognize these proteins and target them to the lysosomes.939 A 28,000-dalton protein called GS28 acts as one of the targeting receptors involved in the recognition of ER-derived vesicles that are destined for fusion with the cis-Golgi membrane.1033 By 1998, more than two dozen different members of the small G protein superfamily (including the Rab and Arf protein families) had been implicated in the regulation of intracellular vesicular trafficking and membrane recognition. The Golgi complex also contains substantial amounts of cholesterol and sphingolipids, making a rising gradient from cis to trans.1117 Various Golgi compartments are defined by the presence of particular enzymes (e.g., glycosidases, glycosyltransferases, and others involved in protein modification or sphingolipid synthesis) that are localized to one or more compartments, often in a graded manner.1118,1119 While all cisternae are fenestrated and display coated buds, the trans-most cisterna produces exclusively clathrin-coated buds, whereas the others display only nonclathrin coated buds.3440 Such distinctions will allow in cyto medical nanorobots with suitable transmembrane chemical sensor tools to readily establish Golgi stack configuration, polarity, and physical extent.
The Golgi stack has other easily detectable asymmetries. Since the GC mediates the flow of secretory proteins from the ER to the cell exterior, the GC displays spatially variant protein and lipid compositional gradients along the Golgi polarity axis. Specifically, the saccule membranes at the forming face resemble those of the ER in morphology and composition -- ~5-6 nm thick membranes defining a relatively narrow ~30-80 nm cisternal space, with ~20% phosphatidylcholine in the membrane. At the maturing pole, the saccule membranes more closely resemble the plasma membrane, ~10 nm thick, with a much wider cisternal space (>100 nm) and with ~10% phosphatidylcholine in the membrane. (Variable membrane thickness is part of the control mechanism for spatially anisotropic budding).1113 Another asymmetry: Swarms of ~50 nm diameter membrane-bound vesicles always cluster on the side of the Golgi stack abutting the ER and along the circumference of a stack near the dilated rims of each cisterna.
Last updated on 20 February 2003