and Jürgen Roth2
Medical University of Vienna, Vienna, Austria
University of Zurich, Zurich, Switzerland
Cytocenter, Centrosome, and Microtubules
The electron micrograph shows the cytocenter of a bone marrow cell of the granulopoietic lineage. It consists of the centrosome with one of the pair of centrioles in the center, abundant radiating microtubules (arrows), and stacks of the Golgi apparatus organized in a circle around the centrosome. In interphase cells, the cytocenter is most commonly located close to the nucleus, which can be seen in the uppermost part of the micrograph. The centrosome is dynamic and, thus, it is important to distinguish between growing and quiescent cells. It contains the centrioles embedded in an amorphous protein matrix and functions as the microtubule-organizing center with gamma-tubulin rings in the matrix, serving as nucleation sites for the growth of microtubules.
Microtubules are essential components of the cytoskeleton and involved in multiple functions such as intracellular transport of organelles, cell migration, and correct segregation of chromosomes during mitosis. Microtubules measure 24 nm in diameter; the wall consists of 13 protofilaments of α- and β-tubulin dimers in a circular array, which polymerize in an end-to-end fashion. The stable minus ends of the microtubules are embedded in the centrosome, and the dynamic plus ends elongate towards the cell periphery forming kinds of tracks within the cells along which organelles are transported with the help of motor proteins. This network is constantly remodeled by growth and sudden shrinkage of the microtubules, a process known as dynamic instability. The centrioles, to which microtubules are anchored, are not only the most prominent structures in the cytocenter but also have a pivotal role for the structural organization of the centrosome. A centriole has the shape of a cylinder of about 0.2 μm length, and the walls consist of nine triplets of microtubules oriented parallel to the longitudinal axis. The microtubules are fused and have a common wall. Only the innermost A-tubule consists of a complete ring of 13 protofilaments; the B- and C-microtubules are crescent-shaped, each consisting of 10 protofilaments. The microtubule triplets are visible in the cross section of the centriole in the center of the micrograph, which also shows cartwheel-shaped structures in its lumen, where centrin (C in the diagram) is known to be localized, and a ring of appendages, where microtubule asters are anchored.
The biogenesis of centrioles either takes place associated with a preexisting centriole or de novo. The diagram (drawn according to Bornens 2002) shows the main components of the centrosome of a cell in the G1 phase containing a differentiated mother centriole (MC) and a daughter centriole (DC). The centrioles are linked by a matrix (dotted line) and embedded in a larger pericentriolar area (outer line, double arrows). Assembly of the matrix is assumed to be triggered by the centrioles through various microtubule-binding proteins (open arrowheads). Juxtacentriolar structures, known as satellite (S), are seen as precursor complexes occurring during centriole duplication. Microtubules are nucleated in the vicinity of both centrioles (Mt), but only the fully differentiated mother centrioles possess appendages, distal appendages (arrow) and subdistal appendages (asterisk), where microtubule asters (filled arrowheads) are anchored. The centriole shown in the micrograph is cross sectioned through its distal part, thus both the centrin core and a corona of subdistal appendages with prominent tips are visible. Part of a microtubule aster is to be seen associated with the right lower appendage.
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Effects of Microtubule Disruption
The involvement of microtubules in main cellular tasks can indirectly be studied by impairment of microtubule function either by disruption of the microtubule network, for example, by treatment with colchicine or nocodacole, or by administration of substances that stabilize microtubules, such as taxol. Because of the important role of microtubules in the intracellular traffic, application of antimicrotubular agents leads to an impairment or block of multiple cellular pathways, including biosynthetic and secretory routes, endocytosis pathways, and transcytosis. Microtubules are required for regular organization and localization of the Golgi apparatus and also have a crucial role in the polarization of cells. Disruption of the microtubule system leads to characteristic cell changes.
In many types of cells, the Golgi apparatus is localized around the centrosome (cf. Fig. 86) and several nonmotor microtubule-binding proteins have been shown to be associated with the Golgi apparatus. The transport of pre-Golgi intermediates from endoplasmic reticulum exit sites in peripheral regions of cells to the cytocenter and finally to the Golgi apparatus also occurs along microtubules and involves minus end-directed motor proteins. After disruption of the cytoplasmic microtubules, the Golgi apparatus loses its characteristic position, becomes vacuolized, and is dispersed throughout the cytoplasm. This is shown in small intestinal absorptive cells of rats 6 h after treatment with colchicine (panels A and B). The Golgi apparatus, which is localized normally in the supranuclear cytoplasm of the absorptive cells (cf. Fig. 128), has disappeared from this site and vacuolized Golgi components are present in uncommon positions close to the basal cell surface (arrowheads). The former Golgi stacks, although redistributed and vacuolized, still contain lipoprotein particles (asterisks), similar to Golgi cisternae of untreated cells. Treatment with colchicine also leads to changes of the typical polarity of the absorptive cells. A brush border of densely packed microvilli, which is usually restricted to the apical cell surfaces, occurs at the basolateral cell surfaces (Bb in panels A and C). It occupies more than 3 % of the basolateral surface at 6 h after colchicine administration. The diagram summarizes the cellular changes occurring after microtubule disruption 6 h after administration of colchicine.
C: cytocenter; GA: Golgi apparatus; G: dispersed Golgi elements; aBb: apical brush border; bBb: basolateral brush border
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