Desmin filaments

Yuan, J., Huiatt, T. W., Liao, C. X., Robson, R. M., and Graves, D.J. (1999). The effects of mono-ADP-ribosylation on desmin assembly-disassembly Determination of the chemical features of bound ADP-ribose that prevent desmin filament formation. 

Nakagawa, H., Ishihara, M., and Ohashi, K (1993). 33-kDa peptides prepared from chicken gizzard smooth muscle bundle both actin and desmin filaments in vitro. J. Biochem. (Tokyo) 114, 623-626. 

Desmin is a cytoplasmic IFP that is characteristically found in muscle cells and in the neoplasms associated with them. In smooth muscle cells, it is seen with cytoplasmic dense bodies and subplasmalemmal dense plaques in striated muscle, desmin filaments are linked to sarcomeric Z disks. 

Schmid E, Osborn M, Rungger-Brandle E, et al. Distribution of vimentin and desmin filaments in smooth muscle tissue of mammalian and avian aorta. Exp Cell Res. 1982 137 329-340. 

These type III intermediate filaments encircle the Z disk and make additional connections to neighboring Z disks. The alignment of desmin filaments with the muscle sarcomere is held in place at the Z disk by a collar of desmin/synemin heteropolymers. 

Intermediate filaments are assemblies of intermediate filament proteins that provide mechanical strength to animal cells. Intermediate filaments include keratins, desmin filaments, vimentin filaments, nuclear lamins, and neurofilaments. The diameter of these filaments (about 10 nm) is intermediate between the thin actin filaments (about 7 nm) and the thicker microtubules (about 25 nm). Networks of cytoplasmic intermediate filaments are found throughout the cytoplasm of most animal cells, with some concentration around the nucleus. The lamin proteins make a network of intermediate filaments, the nuclear lamina, that lies just inside the nuclear membrane. 

Tissue-specific intermediate filaments have been classified into vimentin filaments, glial filaments, neurofilaments, desmin filaments and cytokeratin filaments. Although each type of filament is composed of a different protein, the various proteins demonstrate remarkable sequence homology. Their functions are unknown. There are at least nine different proteins associated with intermediate filaments. 

The leucine zipper DNA-binding proteins, described in Chapter 10, are examples of globular proteins that use coiled coils to form both homo- and heterodimers. A variety of fibrous proteins also have heptad repeats in their sequences and use coiled coils to form oligomers, mainly dimers and trimers. Among these are myosin, fibrinogen, actin cross-linking proteins such as spectrin and dystrophin as well as the intermediate filament proteins keratin, vimentin, desmin, and neurofilament proteins. 

The analytic validity of an abstract parallel elastic component rests on an assumption. On the basis of its presumed separate physical basis, it is ordinarily taken that the resistance to stretch present at rest is still there during activation. In short, it is in parallel with the filaments which generate active force. This assumption is especially attractive since the actin-myosin system has no demonstrable resistance to stretch in skeletal muscle. However, one should keep in mind, for example, that in smooth muscle cells there is an intracellular filament system which runs in parallel with the actin-myosin system, the intermediate filament system composed of an entirely different set of proteins, (vimentin, desmin, etc.), whose mechanical properties are essentially unknown. Moreover, as already mentioned, different smooth muscles have different extracellular volumes and different kinds of filaments between the cells. 

Desmin Lies alongside actin filaments Attaches to plasma membrane (plasma-lemma). 

In addition to actin and myosin, other proteins are found in the two sets of filaments. Tropomyosin and a complex of three subunits collectively called troponin are present in the thin filaments and play an important role in the regulation of muscle contraction. Although the proteins constituting the M and the Z bands have not been fully characterized, they include a-actinin and desmin as well as the enzyme creatine kinase, together with other proteins. A continuous elastic network of proteins, such as connectin, surround the actin and myosin filaments, providing muscle with a parallel passive elastic element. Actin forms the backbone of the thin filaments [4]. The thin... 

The five intermediate filaments and their respective tissues are listed in Table 3. Only the intermediate filament, cytokeratin, is selected as useful in the initial classification of tumors. The other intermediate filaments can cause diagnostic confusion because (1) they are usually not expressed in their poorly differentiated counterparts (especially GFAP, NFP, and Desmin) and (2) they are often coexpressed on many types of tumors. Poorly differentiated neuroectodermal tumors may often express more than two intermediate filaments. Vimentin demonstrates the most lineage infidelity. 

Fewer antibodies are available to characterize these tumors than those from the other categories. Table 12 lists the most useful antigens that can be detected in routinely processed tissues. Antibodies to desmin, an intermediate filament, are very specific for muscle tumors. Because of its sensitivity to fixation and its absence in the early differentiation of muscle cells, desmin is often difficult to detect in muscle sarcomas. 

The components of the intermediate filaments belong to five related protein families. They are specific for particular cell types. Typical representatives include the cytokeratins, desmin, vimentin, glial fibrillary acidic protein (GFAP), and neurofilament. These proteins all have a rod-shaped basic structure in the center, which is known as a superhelix ( coiled coil see keratin, p. 70). The dimers are arranged in an antiparallel fashion to form tet-ramers. A staggered head-to-head arrangement produces protofilaments. Eight protofilaments ultimately form an intermediary filament. 

The C-protein (thick filaments), myomesin (M-line protein), and a-actinin (Z-line protein)110113114 each provide 2% of the protein in the myofibril. Less than 1% each of 11 or more other proteins may also be present within the sarcomere.86115 Several of these, including the cytoskeletal proteins desmin and vimentin, and synemin surround the Z-discs.116/116a... 

McLachlan, A. D., and Stewart, M. (1982). Periodic charge distribution in the intermediate filament proteins desmin and vimentin./. Mol. Biol. 162, 693-698. 

In striated skeletal and cardiac muscle, the desmin IF network forms an exosarcomeric lattice surrounding the myofibrils. Parallel filaments link Z-disks within a myofibril, and a prominent series of transverse filaments link neighboring myofibrils at the level of the Z-disks (Price and... 

Fig. 4. Structure of striated muscle costameres and the DPC. A single membrane-associated costamere from a portion of a striated muscle fiber is magnified above to show the components of the dystrophin-associated protein complex that are involved in linking desmin intermediate filaments (IFs) to the muscle cell membrane. Additional actin-associated proteins present at these sites (including vinculin, talin, spectrin, and ankyrin) are not shown here. In addition to components of the DPC, plectin has also been localized to costameres, and likely contributes to linking desmin IFs to actin-associated structures.

Syncoilin is highly expressed in skeletal and cardiac muscle and is localized to the neuromuscular junction, sarcolemma, and Z-lines. Likewise, desmuslin is expressed in heart and skeletal muscle and localized at Z-lines. It was shown that syncoilin and desmin interact directly, but do not coassemble into filaments in fact, evidence suggests that syncoilin does not participate in filament formation at all. It was proposed that syncoilin helps anchor the desmin IF network at the sarcolemma and the neuromuscular junction (Poon et al, 2002). More recent work has analyzed patients with a desmin-related cardiomyopathy in which patients with desmin accumulation also exhibit an upregulation of syncoilin and accumulation of other elements of the DPC. These defects were correlated with a disappearance of both o-dystrobrevin-l and neuronal nitric oxide... 

The role of the IF, and particularly the keratin filament system, in resisting the forces of mechanical stress has been well established. However, IFs also play a role in countering metabolic stress. Perhaps the best example is the cytoprotective role played by the simple epithelial keratins, K8/18. However, vimentin, desmin, peripherin, GFAP, the lens proteins phakinin, and filensin and other keratins have also been shown to associate with members of the small heat shock protein (HSP) family, including HSP27 and aB-crystallin (reviewed in Coulombe and Wong, 2004 Marceau et al., 2001 Nicholl and Quinlan, 1994). 

Chen, F., Chang, R., Trivedi, M., Capetanaki, Y., and Cryns, V. L. (2003). Caspase proteolysis of desmin produces a dominant-negative inhibitor of intermediate filaments and promotes apoptosis. J. Biol. Chem. 278, 6848-6853. 

Georgatos, S. D., Weber, K., Geisler, N., and Blobel, G. (1987). Binding of two desmin derivatives to the plasma membrane and the nuclear envelope of avian erythrocytes Evidence for a conserved site-specificity in intermediate filament-membrane interactions. Proc. Natl. Acad. Sci. 84, 6780-6784. 

Granger, B. L., and Lazarides, E. (1980). Synemin A new high molecular weight protein associated with desmin and vimentin filaments in muscle. Cell 22, 727-738. 

Hijikata, T., Murakami, T., Ishikawa, H., and Yorifuji, H. (2003). Plectin tethers desmin intermediate filaments onto subsarcolemmal dense plaques containing dystrophin and vinculin. Histochem. Cell Biol. 119, 109-123. 

Langley, R. C., Jr., and Cohen, C. M. (1986). Association of spectrin with desmin intermediate filaments./ Cell Biochem. 30, 101-109. 

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