Actinins

A comparison of the amino acid sequences of dystrophin, a-actinin, and spectrin. The potential hinge segments in die dystrophin structure are indicated. 

FIGURE 17.20 A schematic drawing of the four-helix cluster model for a-actinin and spectrin. Helix 1 is long and is postulated to lie at an angle with respect to the long axis of the repeated domain. 

Davison, M., and Critchley, D., 1988. o -Actinin and the DMD protein contain. spectrin-like repeats. C>//52 159-160. 

Davison, M., et al., 1989. Structural analysis of homologous repeated domains in ct-actinin and. spectrin. International Journal of Biological Macromolecules 11 81—90. 

By binding to F-actin, actin binding proteins (ABPs) stabilize F-actin or regulate its turnover. Known ABPs are proteins such as a-actinin, talin, tensin, filamin, nexilin, fimbrin, and vinculin. 

Cytokinesis (cell division) in animal cells involves the progressive formation in telophase of a furrow between the two daughter cells in the equator of the mitotic spindle. Immunofluorescent staining of the cortical cytoplasm at the site of the contraction ring reveals an abundance of actin as well as myosin, a-actinin, and filamin (Fishkind and Wang, 1995). Cytokinesis is highly sensitive to actin-myosin inhibitors such as cytochalasin and phalloidin. 

Pointed-end-capping proteins are acumentin (65 kD), spectrin (220-260 kD), and p-actinin (37 kD). They also regulate the length of actin filaments. 

Stress fibers are parallel bundles of actin filaments that develop in the cytoplasm of fibroblasts from the cortical actin network in response to mechanical tension. These often bind to the plasma membrane at focal contacts and, through transmembrane linker glycoproteins, to the extracellular matrix. Thus, actin filaments of stress fibers indirectly Join to the inner face of the plasma membrane through molecular assemblies of attachment proteins, which include an actin-capping protein, a-actinin, vinculin, and talin (Small, 1988). 

Bundles of parallel actin filaments with uniform polarity. The microvilli of intestinal epithelial cells (enterocytes) are packed with actin filaments that are attached to the overlying plasma membrane through a complex composed of a 110-kD protein and calmodulin. The actin filaments are attached to each other through fimbrin (68 kD) and villin (95 kD). The actin bundles that emerge out of the roots of microvilli disperse horizontally to form a filamentous complex, the terminal web, in which several cytoskeletal proteins, spectrin (fodrin), myosin, actinin, and tropomyosin are present. Actin in the terminal web also forms a peripheral ring, which is associated with the plasma membrane on the lateral surfaces of the enterocyte (see Figure 5, p. 24). 

Maciver, S.K. (1991). The actin filament severing protein actophorin promotes the formation of rigid bundles of actin filaments crosslinked with a-actinin. J. Cell Biol. 115, 1621-1628. 

Wallraff, E., Schleicher, M., Modersitzki. M Reiger, D., Isenberg, G., Gerish, G. (1986). Selection of Dictyostelium mutants defective in cytoskeletal protein Use of an antibody that binds to the ends of alpha-actinin rods. EMBO J. 5,61-67. 

Another actin binding protein, the large 100 kDa a-actinin, crosslinks actin filaments together at the dense bodies and near the points of actin filament attachment to the cell membranes, a-actinin is also associated with still another actin binding protein, vinculin, which may stabilize both the Z-line like dense bodies and the membrane attachments. 

The superstructure of smooth muscle actin filaments is differentiated from those of striated muscle by the absence of the troponins and the lateral organization by association of the filaments with dense bodies instead of with the Z-line. How these differences are encoded is again not at all clear. However, the myofibrillar structure and the alignment of the alternating actin and myosin filaments is apparently due primarily to dense bodies and the actin-actinin macrostructures. As the bent dumbbell shaped actins assemble into filaments they are all oriented in the same direction. The S-1 fragments of myosin will bind to actin filaments in vitro and in... 

In severe neonatal nemaline myopathy virtually every muscle fiber shows multiple rods and all muscle fiber types are affected. However in juvenile cases, two different patterns of fiber type involvement are seen. In one there is a clear size difference between type 1 fibers, which are abnormally small (hypotrophic or atrophic) and which contain numerous nemaline rods, and type 2 fibers, which are either of normal diameter or hypertrophic and contain few, if any, nemaline rods. Other patients show a gross predominance of type 1 muscle fibers, again with rods virtually confined to this fiber type. These findings may be explicable in terms of the involvement of isoforms of a-actinin specific to slow and fast muscle fiber types. 

A number of additional proteins play various roles in the structure and function of muscle. They include titin (the largest protein known), nebufin, a-actinin, desmin, dystrophin, and calcineurin. Some properties of these proteins are summarized in Table 49-2. 

Smooth muscles have molecular structures similar to those in striated muscle, but the sarcomeres are not aligned so as to generate the striated appearance. Smooth muscles contain a-actinin and tropomyosin molecules, as do skeletal muscles. They do not have the troponin system, and the fight chains of smooth muscle myosin molecules differ from those of striated muscle myosin. Regulation of smooth muscle contraction is myosin-based, unlike striated muscle, which is actin-based. However, like striated muscle, smooth muscle contraction is regulated by Ca. ... 

Ursitti, J. A., Kotula, L., DeSilva, T. M., Curtis, P. J. and Speicher, D. W. Mapping the human erythrocyte P-spectrin dimer initiation site using recombinant peptides and correlation of its phasing with the a-actinin dimer site. /. Biol. Chem. 271 6636-6644,1996. 

The NR2 subunit of the NMDA receptor binds to PDZ domains of PSD95 with its cytoplasmic C-terminus. PSD95 also binds a-actinin, which again binds to filamentous actin (F-actin), a main cytoskeletal protein in dendritic spines. In this manner PSD95 anchors the NMDA receptor to the cytoskeleton of the dendritic spine. 

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... 

Vinculin is one of a number of proteins that bind the actin network to the plasma membrane. It is a 130-kDa protein that is phosphorylated at a tyrosine residue by a kinase that is controlled by the src gene. Vinculin function is Ca2+-dependent, and it is found in close association with a-actinin. 

Yuruker, B., Niggli, V. (1992). a- Actinin and vinculin in human neutrophils Reorganization during adhesion and relation to the actin network. /. Cell Sci. 101,403-14. 

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