A-actinin molecules

In the Z-band, the a-actinin molecules form cross-links between anti-parallel actin filaments. In muscle cross-sections (Fig. 1 IB, C) the square Z-band structure appears in two forms, the basketweave and the small square lattice. These appearances seem to depend on the shape of the cross-links between adjacent anti-parallel actin filaments (called up [U] and down [D] in Figs. 11-14). Some authors believe that the appearance depends on the physiological state of the muscle (e.g., Goldstein et ah, 1988), although this is not certain. A possible mechanism relating the two may be that the small square lattice is simply a basketweave in which the a-actinin cross-links have become bent (Yamaguchi et al., 1985). 

Fig. 11. The structure of a-actinin and the two vertebrate Z-band lattices. (A) The ubiquitous protein a-actinin is an anti-parallel homodimer. Each 100 KDa monomer comprises four central spectrin repeats (SI to S4) an EF-hand domain and two calponin homology domains (CH) at the N-terminus. The EF-hand domains bind calcium in non-muscle cells. One a-actinin molecule binds two actin filaments via the calponin homology domains. a-Actinin binds titin via EF-hand domains. (B, C) The Z-band is the site where actin filaments from adjacent sarcomeres overlap in a tetragonal lattice and are crosslinked by a-actinin molecules. The polarity and origin of the actin filaments is indicated by U (up) and D (down). The appearance of the Z-band in cross-section is typically basketweave-like (B) or small square-like (G). The appearance is reported to transform between the two appearances depending on the state of the muscle.

In vitro, o -actinin and filamin bind actin, the major protein of thin filaments. One a-actinin molecule binds to two actin filaments, one from each side of the Z-disk. Four a-actinin molecules bind to each actin filament at 90° angles, so that the actin filaments are bound into the Z-disks in a square array, although in most of the length of the sarcomere their arrangement is hexagonal. Desmin, an intermediate filament protein, forms a network from one Z-disk to the next across the myofibril. Such links, aided by attachment of desmin and dystrophin to the sarcolemma, help hold the sarcomere structure in... 

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. ... 

Actin filaments and titin molecules are cross-linked in the Z-disc via the Z-line protein a-actinin. 

Carpen, O., Pallai, P., Staunton, D.E., Springer, T.A., 1992. Association of intercellular adhesion molecule-1 (ICAM-1) with actin-containing cytoskeleton and a-actinin. J. Cell Biol. 118, 1223-1234. 

Proteins of the M-line and Z-disc. The M-line region contains the structural protein myomesin, which binds to both titin and myosin and holds the two together. Fast skeletal and cardiac fibers also confain another M-protein, which may bridge between myosin filaments. Both the C-terminal region of nebulin and the N termini of pairs of titin molecules meet in the Z-disc, where they are bound into a lattice containing a-actinin 4 and other proteins (Fig. 

Other M. p. are filamin, M, 250,000, which binds ac-tin vinculin, 130,000, which is part of the Z line, and titin (or connectin), M, 250,000, found in cardiac and skeletal muscle. The giant, single molecule of 11-tin forms a filament extending from the M-line to the Z-line in the striated muscle sarcomere. In smooth muscle, a-actinin, vinculin and filamin anchor the thin filaments to the cell membrane. [R.M.Bagby in Newman Stephens (eds.) Biochemistry of Smooth Muscle (CRC Press, Boca Raton, 1983) pp.1-84 R.M.Dowben J.W.Shay (eds.) Cell and Muscle Motility Vol.4 (Plenum, New York, 1983) S.B.Marston C.W.J. Smith J. Muscle Res Cell Motil. 6 (1985) 669-708 K.Wang in Cell and Muscle Motility (ed. J.W.Shay) Vol.6 (Plenum, New York, 1985) pp. 315-369 J.-P.Jin J. Biol. Chem. 270 (1995) 6908-6916 B.J.Agnew etal. J. Biol. Chem. 27 (1995) 17582-17587 A.S.Rovner etal. J. Biol. Chem. 270 (1995) 30260-30263]... 

Alpha-Actinin is a rod-like (3-4 nmx 30-40 nm) cytoskeletal protein belonging to the same family as spectrin, dystrophin and utrophin. a-Actinin is a homodimer with a subunit molecular weight of 94-103 kDa in which the subunits are antiparallel in orientation. The molecule can be devised into three domains, an N-terminal actin binding domain (approximately residues 1-245), four internal 120 residue repeats, and a C-terminal region containing two EF-hand Ca -binding motifs (Baron et al. 1987, Blanchard et al. 1989). Apart from actin, a-actinin has been reported to bind to the cytoskel-... 

The function of spectrin superfamily proteins is particularly evident when taken in context of their cellular localization. They often form flexible links or structures that allow interactions with the cellular cyto-skeletal architecture and the membrane. In both spectrin and dystrophin, such a function is performed, but the spectrin repeats of these molecules are also able to interact with actin and contribute to binding. A portion of the dystrophin rod domain that spans residues 11-17 contains a number of basic repeats that allow a lateral interaction with filamentous actin (Rybakova et al., 2002). The homologous utrophin can also interact laterally with actin. This interaction is distinct from that of dystrophin, as the utrophin rod domain lacks the basic repeat cluster and associates with actin via the first ten spectrin repeats (Rybakova et al., 2002). /3-Spectrin also exhibits an extended contact with actin via the first spectrin repeat. In this situation, it was found that the extended contact increased the association of the adjacent ABD with actin (Li and Bennett, 1996). In conjunction with this interaction, it has been found that the second repeat is also required for maximal interaction with adducin (Li and Bennett, 1996), a protein localized at the spectrin-actin junction that is believed to contribute to the assembly of this structure in the membrane skeletal network (Gardner and Bennett, 1987). In the erythrocyte cytoskeletal lattice, /3-spectrin interacts with ankyrin, which in turn binds to the cytoplasmic domain of the membrane-associated anion exchanger. This indirect link to the cellular membrane occurs via repeat 15 of /3-spectrin (Kennedy et al., 1991) and is largely responsible for the attachment of the spectrin-actin network to the erythrocyte membrane (reviewed in Bennett and Baines, 2001). A much larger number of direct links to transmembrane proteins have been determined for the spectrin repeats of o-actinin (reviewed in Djinovic-Carugo et al, 2002). 

Mimura, N., and Asano, A. (1987). Further characterization of a conserved actin-binding 27-kDa fragment of actinogelin and alpha-actinins and mapping of their binding sites on the actin molecule by chemical cross-linking. J. Biol. Chem. 262, 4717-4723. 

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