Microtubule systems

This very brief overview provides only a glimpse of the complexity of microtubule systems, but the necessity to understand the underlying protein chemistry of microtubule components should be evident. 

Proteins and Emymes Associated with Microtubule Systems... 

In the course of our synthetic efforts, we discovered a new, unnatural conformational isomer of the VBL piperidine ring (see Chapter 2, this volume, for details). This compound is inactive with the microtubule system in vitro and is poorly cytotoxic to cultured tumor cells (Fig. 5b). Therefore, the functional determinism of the C-20 position of VBL-like molecules mediates reactions, as yet unknown, that are dependent on the binary alkaloid structure and on the natural stereochemical configuration at C-16 and C-14 as well as on the conformation of the cleavamine moiety. 

The structure-function relationship of the indole-indoline binary alkaloids was relegated to obscurity until the recent achievement of methodologies for their complete syntheses (see Chapter 2, this volume). Our work with C-20 congeners of VBL has established that the complex interactions between this molecule and tubulin or microtubules can be modified by structural alteration. The various, concentration-dependent reactions of VBL with the microtubule system in vitro are sensitive to subtle modifications at a single molecular locus. In addition, these reactions are distinctive on a mechanistic level as seen from the unique activity profiles of most of our C-20 alkyl congeners. At first light, we can look toward the future with secured optimism. 

Ultrastructural changes and giant platelets are seen in May-Hegglin anomaly. An alteration in the platelet microtubule system affects platelet structure, although platelet aggregation and interaction with vWF is normal. The lack of platelet... 

In addition to being an essential component of the mitotic spindle, and being required for the maintenance of cell shape, microtubules are involved in a wide variety of cellular activities, such as cell motility and communication between organelles within the cell. Any disruption of the equilibrium within the microtubule system would be expected to disrupt cell division and normal cellular activities in which microtubules are involved. 

These are Ca -binding proteins found in the brain and the central nervous system, which belong to the same branch of the calmodulin family as the intestinal proteins, to which they are closely related. Both contain one variant and one normal " site for Ca . The SlOO protein exists in two forms, a and b. Binding of calcium results in conformational change. The SlOOb protein also binds two Zn ions, with conformational change, and with higher affinity than Ca. Zn is involved with the tubulin microtubule system in brain. SlOOb may be associated with this process. 

The more potent cis isomers were also assayed for inhibition of tubulin polymerization, to investigate the correlation cjdotoxic activity/ interaction with the microtubule system. 

This chapter discusses muscle, an actin filament system, and cilia, a microtubule system. These do not typify all contractile systems. In some actin filament systems, movement occurs in the absence of myosin, being driven... 

Microtubule systems are used in the cell for many other functions, such as transport of organelles and vesicles, and separating genetic material on the mitotic spindle and other motile events of the cell cycle. Substances that interfere with microtubule growth or turnover, or with microtubule interaction with motor proteins, will disrupt these... 

Langmuir-Blodgett films, vesicle, and lipid microtubule systems (Fig. la) will not be covered in this review, even though micelle and micro emulsion systems have historically been assigned phase designations (e.g., Li and L2, respectively) despite the fact that such systems do not have periodic order [2-4],... 

See also Microtubule Systems, Intracellular Transport of Materials... 

See also Microtubule Systems, Motions of Cilia and Flagella, Intracellular Transport of Materials, Actin and Myosin... 

Substances able to interact with tubulin/microtubule system represent a potential inhibitor of cell replication. 

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