Cytoskeletal elements

FIGURE 17.1 Micrographs and electron micrographs of cytoskeletal elements, cilia, and flagella (a) microtnbnles, (b) rat sperm tail microtnbnles (cross-section),... 

Smooth muscles, as the name implies, do not contain sarcomeres. In fact, it was initially difficult to demonstrate the presence of thick filaments in smooth muscle, although their presence is now well-established. On the other hand, it is very difficult to demonstrate thick filaments in highly motile cells, such as macrophages and neutrophils, and this may reflect the necessity to rapidly form and redistribute cytoskeletal elements during migration. Thick filaments in smooth muscles appear to be considerably longer than those in striated muscles. They run diagonally in smooth muscle cells and attach to the membrane at structures known as dense bodies. Thus, there is a cork-screw effect when smooth muscles contract (Warshaw etal., 1987). 

Several independent laboratories have now demonstrated that both lithium and valproate (VPA) exert complex, isozyme-specific effects on the PKC (protein kinase C) signaling cascade (reviewed in [3, 5, 11-13]). Not surprisingly, considerable research has recently attempted to identify changes in the activity of transcription factors known to be regulated (at least in part) by the PKC signaling pathway - in particular the activator protein 1 (AP-1) family of transcription factors. In the CNS, the genes that are regulated by AP-1 include those for various neuropeptides, neurotrophins, receptors, transcription factors, enzymes involved in neurotransmitter synthesis, and proteins that bind to cytoskeletal elements [14]. 

Both the composition and organization of cytoskeletal elements in axons and dendrites become specialized early in differentiation 131... 

Methods for visualizing individual neurons and glia in vivo have depended for more than 100 years on histo-chemical reactions with cytoskeletal elements and even now these methods have not been surpassed. Because cytoskeletal structures play a particularly prominent role in the nervous system, cytoskeletal proteins represent a large fraction of total brain protein, comprising perhaps a third or more of the total. In fact, much of our knowledge about cytoskeletal biochemistry is based on studies of proteins purified from brain. The aims of this chapter are twofold first to provide an introduction to the cytoskeletal elements themselves and second to examine their role in neuronal function. Throughout, the emphasis will be on the cytoskeleton as a vital, dynamic component of the nervous system. 

While each set of cytoskeletal elements has a distinctive spectrum of composition, stability and distribution, all three interact with each other. They have complementary functions and may be coordinately regulated. Such interactions can be seen during development of the nervous system, in mature neuron/glia interactions and in neuropathologies. 

Cytoplasmic and cytoskeletal elements move coherently at slow transport... 

FIGURE 28-5 Schematic illustration of the movement of cytoskeletal elements in slow axonal transport. Slow axonal transport represents the movement of cytoplasmic constituents including cytoskeletal elements and soluble enzymes of intermediary metabolism at rates of 0.2-2 mm/day which are at least two orders of magnitude slower than those observed in fast axonal transport. As proposed in the structural hypothesis and supported by experimental evidence, cytoskeletal components are believed to be transported down the axon in their polymeric forms, not as individual subunit polypeptides. Cytoskeletal polypeptides are translated on cytoplasmic polysomes and then are assembled into polymers prior to transport down the axon in the anterograde direction. In contrast to fast axonal transport, no constituents of slow transport appear to be transported in the retrograde direction. Although the polypeptide composition of slow axonal transport has been extensively characterized, the motor molecule(s) responsible for the movement of these cytoplasmic constituents has not yet been identified. 

Cytoplasmic and cytoskeletal elements move coherently at slow transport rates. Two major rate components have been described for slow axonal transport, representing movement of cytoplasmic constituents including cytoskeletal elements and soluble enzymes of intermediary metabolism [3]. Cytoplasmic and cytoskeletal elements in axonal transport move with rates at least two orders of magnitude slower than fast transport. 

The incidence of ovarian tumors in mice, guinea pigs, and rabbits increased after 3 years of chronic irradiation at doses as low as 1.1 mGy daily (Lorenz et al. 1954). Unlike other tumors, the induction of ovarian tumors depended on a minimum total dose and seemed to be independent of a daily dose (Lorenz et al. 1954). Radiation-induced neoplastic transformation of hamster cells may be associated initially with changes in expression of the genes modifying cytoskeletal elements (Woloschak et al. 1990b). 

Woloschak, G.E., P. Shearin-Jones, and C.M. Chang-Liu. 1990b. Effects of ionizing radiation on expression of genes encoding cytoskeletal elements kinetics and dose effects. Molec. Carcinogen. 3 374-378. 

I have included cytoskeletal elements for completion. By cytoskeletal , I mean any molecular mechanisms that play a role in holding the various elements of the SR in their correct relationship with the plasma membrane and its various channels,... 

Neurons possess a cell body (also referred to as a soma or perikaryon), which consists of a nucleus surrounded by cytoplasm and membrane. The survival of the rest of the neuron is dependent upon the integrity of the cell body. Axons and dendrites are both processes that extend from the cell body. Also located in the cell body are the Golgi apparatus, smooth ER, rough ER, and mitochondria. Cytoskeletal elements—microtubules and neurofilaments—are also present. 

Neuroanatomical and neuropathological basis of Alzheimer s disease Histological features of Alzheimer s disease include neuritic plaques and neurofibrillary tangles (Boiler and Duyckaerts 1997). Neuritic plaques are composed of extracellular deposits of j8-amyloid protein and apolipoprotein E and are found primarily in neocortex. j8-amyloid is derived from an amyloid precursor protein, and is suspected to be a chief causal factor in Alzheimer s disease pathology (Samuel et al. 1997). Neurofibrillary tangles are clusters of protein fibers found in the cell body and composed of tau protein, which normally serves as a cytoskeletal element. Neurofibrillary tangles progress from entorhinal cortex to hippocampus, and then to neocortical areas. 

Another example of how whole-mount technology has facilitated the study of three-dimensional arrays of filamentous networks is the visualization of cytoskeletal elements within the context of tissues. It is only through whole-... 

The principal cytoskeletal proteins in non-muscle cells are actin, tubulin, and the components of intermediate filaments. Actin can exist either as monomers ( G-actin ) or polymerized into 70 A diameter double filament ( F-actin ). Polymerized actin usually is localized at the margins of the cells, linked by other proteins to the cell membrane. In contrast, tubulin forms hollow filaments, approximately 250 A in diameter, that are distributed within a cell in association, generally, with cell organelles. Stabilized microtubule structures are found in the flagella and cilia of eucaryotic cells however, in other instances - examples being the mitotic apparatus and the cytoskeletal elements arising in directed cell locomotion - the microtubules are temporal entities. Intermediate filaments, which are composed of keratin-like proteins, are approximately 100 A thick and form stable structural elements that impart rigidity, for example, to nerve axons and epithelial cells. 

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