Role of microtubules in the organization of the Golgi complex

The Golgi complex of mammalian cells is composed of cisternal stacks that f unction in processing and sorting of membrane and luminal proteins during t ransport from the site of synthesis in the endoplasmic reticulum to lysosom es, secretory vacuoles, and the cell surface. Even though exceptions are fo und, the Golgi stacks are usually arranged as an interconnected network in the region around the centrosome, the major organizing center for cytoplasm ic microtubules. A close relation thus exists between Golgi elements and mi crotubules (especially the stable subpopulation enriched in detyrosinated a nd acetylated tubulin). After drug-induced disruption of microtubules, the Golgi stacks are disconnected from each other, partly broken up, dispersed in the cytoplasm, and redistributed to endoplasmic reticulum exit sites. De spite this, intracellular protein traffic is only moderately disturbed. Fol lowing removal of the drugs, scattered Golgi elements move along reassembli ng microtubules back to the centrosomal region and reunite into a continuou s system. The microtubule-dependent motor proteins cytoplasmic dynein and k inesin bind to Gels membranes and have been implicated in vesicular transpo rt to and from the Golgi complex. Microinjection of dynein heavy chain anti bodies causes dispersal of the Golgi complex, and the Golgi complex of cell s lacking cytoplasmic dynein is likewise spread throughout the cytoplasm. I n a similar manner, kinesin antibodies have been found to inhibit Golgi-to- endoplasmic reticulum transport in brefeldin A-treated cells and scattering of Golgi elements along remaining microtubules in cells exposed to a low c oncentration of nocodazole. The molecular mechanisms in the interaction bet ween microtubules and membranes are, however, incompletely understood. Duri ng mitosis, the Golgi complex is extensively reorganized in order to ensure an equal partitioning of this single-copy organelle between the daughter c ells. Mitosis-promoting factor, a complex of cdc2 kinase and cyclin B, is a key regulator of this and other events in the induction of cell division. Cytoplasmic microtubules depolymerize in prophase and as a result thereof, the Gels stacks become smaller, disengage from each other, and take up a pe rinuclear distribution. The mitotic spindle is thereafter put together, ali gns the chromosomes in the metaphase plate, and eventually pulls the sister chromatids apart in anaphase. In parallel, the Golgi stacks are broken dow n into clusters of vesicles and tubules and movement of protein along the e xocytic and endocytic pathways is inhibited. Using a cell-free system, it h as been established that the fragmentation of the Golgi stacks is due to a continued budding of transport vesicles and a concomitant inhibition of the fusion of the vesicles with their target membranes. In telophase and after cytokinesis, a Golgi complex made up of interconnected cisternal stacks is recreated in each daughter cell and intracellular protein traffic is resum ed. This restoration of a normal interphase morphology and function is depe ndent on reassembly of a radiating array of cytoplasmic microtubules along which vesicles can be carried and on reactivation of the machinery for memb rane fusion. (C) 1999 Academic Press.