Cell Microtubules

The role of microtubules in secretion is more clearly defined. Colchicine and vinblastine inhibit secretion, even in cytochalasin-B-treated cells, and D2O (which promotes tubulin assembly) enhances secretion in cytochalasin-treated cells. Microtubules may also be necessary for the translocation of phagocytic vesicles from the neutrophil periphery into the central region of the cytoplasm. Drugs affecting microtubule assembly may inhibit particle-induced oxidase activation or else increase oxidase activation in response to soluble agents such as fMet-Leu-Phe. 

Stockert JC, Juarranz A, Villanueva A, Canete M (1996) Photodynamic damage to HeLa cell microtubules induced by thiazine dyes. Cancer Chemother Pharmacol 39 167-169. 

Microtubules, especially those that make up the mitotic spindle, are in a delicate state of balance between assembly and disassembly. This is because both the formation of the spindle and the movement of chromosomes to opposite spindle poles depend on carefully coordinated extension or shrinkage at both ends of the microtubules in the spindle. The end of a microtubule that terminates with /1-tubulin is more dynamic than the other end, which has an a-tubulin monomer as its final subunit. In cells, microtubules usually grow out from some sort of organizing... 

In the fine structure of cells, microtubules make up fibers such as the spindle fibers that attach to centromeres of chromosomes to pull chromatids apart during mitosis and meiosis. Microtubules function in a number of cellular processes, including motility of cells and subcellular components. Microtubules assemble into tubulin, a substance that can change the shape of cells. 

In line with its effects on mbulin polymerization in vitro (i.e., in an excellular context), the prevention of cold-induced depolymerization of micrombules by epothilones has also been demonstrated in cells. Microtubule stabilization in intact cells (as well as cancer cell growth inhibition, vide infra), however, is observed at strikingly lower concentrations than those required for the induction... 

Microtubules similar to those found in flagella are also present in the cytoplasm. Together with thinner microfilaments of several kinds they form an internal cytoskeleton that provides rigidity to cells. Microtubules also form the "spindle" of dividing cells. In nerve axons (Chapter 30) the microtubules nm parallel to the length of the axons and are part of a mechanical transport system for cell constituents. 

These initial observations of 2,5-HD-induced alterations in microtubule assembly led to the articulation of a tubulin-based hypothesis for 2,5-HD-induced testicular injury as follows [1] intoxication with 2,5-HD alters microtubule assembly kinetics, [2] altered assembly produces changes in the number and length of Sertoli cell microtubules which compromises Sertoli cell function, and [3] malfunctioning, nonsupportive Sertoli cells dismpt germ cell maturation resulting in testicular atrophy (25). 

Microtubule networks promote targeted secretion in a number of polarized cell types, including MDCK cells (43, 44) and Caco-2 cells (43). Sertoli cell microtubules are oriented parallel to the long axis of the cell and, like those of many polarized cells, arise from nucleation centers located in the apical aspect of the cell (45, 46), not from the basally located centrosome (47). 

Whatever the signals are that trigger germ cell apoptosis, the initiating event could be a deficiency of a survival factor due to failure of the normal Sertoli cell microtubule-dependent formation of seminiferous tubule fluid. One important survival factor made by Sertoli cells and required by germ cells is stem cell factor (SCF) (82). 

Although indirect evidence supports the assertion that 2,5-HD alters Sertoli cell microtubule-dependent transport and inhibits seminiferous tubule fluid formation, the molecular connections between these processes remain to be elucidated. 

Historically, insight into the role of Sertoli cell microtubules in promoting spermatogenesis has been gleaned from analyzing the actions of known microtubule disrupters in the testis. Both colchicine and taxol lead to defects in spermiation and residual body elimination, activities attributed to Sertoli cells (105-107). Because microtubules are present in all cells, however, these studies cannot rule out potential actions on other cellular targets, particularly on the germ cells themselves. 

A true test of this model requires selective access to Sertoli cell microtubule networks in vivo, independent of direct effects on germ cells. Such a mechanism precludes toxicant or pharmacologic manipulations of microtubules, which exert effects globally. Cell-type specificity can only be afforded by molecular interventions that are capable of being either delivered or expressed in subsets of cells. 

This model also has the potential to address more fundamental questions of Sertoli cell microtubule organization and Sertoli-germ cell interdependence. The mechanism of microtubule nucleation in ary polarized epithelial cell is presently... 

Richburg JH, Redenbach DM, Boekel-heide K. 1994. Seminiferous tubule fluid secretion is a Sertoli cell microtubule-dependent process inhibited by 2,5-hexa-nedione exposure. Toxicol. Appl. Pharmacol. 128 302-9... 

Redenbach DM, Hall ES, Boekelheide K. 1995. Distribution of Sertoli cell microtubules, microtubule-dependent motors, and the Golgi apparatus before and after tight junction formation in developing rat testis. Microsc. Res. Tech. 32 504-19... 

The general field with which this review is concerned is currently one of the most exciting in chemical physics, the study of kinetic processes in systems of finite size and/or of restricted dimensionality. Problems ranging from the study of organized molecular assemblies (micelles, vesicles, microemulsions), biological systems (cells, microtubules, chloroplasts, mitochondria), structured media such as clays and zeolites, and nucleation phenomena in finite domains are among those under active investigation. 

In some animal cells, microtubules radiate out from a single microtubule-organizing center lying at the cell center (see Figure 5-33). Intact microtubules appear to be necessary for endoplasmic reticulum and Golgi membranes to form into organized structures. 

In cells, microtubule assembly depends on other proteins as well as tubulin concentration and temperature. What types of proteins Influence microtubule assembly In vivo, and how does each type affect assembly ... 

Microtubules are cytoskeletal polymers consisting of repeatii a/ -tubulin heterodimers and a variety of minor components known as microtubule-associated proteins which are important for the regulation and distribution of microtubules in the cell Microtubules play the key role in many vital cellular aaivities such as mitosis, intracellular vesicle tnmsport, o miza-tion and positioning of membranous organelles, and determination of cell shape and motility. 

FIGURE 5.3 The AFM two-dimensional image (a) of nanoparticles on the basis Fe (acacy 8C6 (HjO) formed on the hydrophobic surface of modified silicone, (b) The section of a circular shape with fixed length and orientation is about 50-80 nm. (c) The structure of the cell microtubules. 

The section of a circular shape with fixed length and orientation is about 50-80 nm (b), (c) The structure of the cell microtubules. 

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