Proteins a-actinin

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). 

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.

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

The molecular mechanisms that couple the contractile filaments to the dense bodies are not established. Dense bodies contain the actin-cross-linking protein, a-actinin, as do the Z-lines of skeletal muscle. Dense bodies also contain actin and probably calponin, although it is currently unclear whether the a and y ("smooth muscle ) isoforms of actin (See Section 4.2) are both present in dense bodies or only the p "non-muscle" isoform (Small 1995, North et al 1994a, 1994b, Mabuchi et d 1996). Ultras-tructural and biochemical data obtained by Mabuchi et al (1997) suggests that one function of calponin may be to couple actin filaments and intermediate filaments at dense bodies. 

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. 

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. 

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. 

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. 

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. 

In addition to the above proteins, a number of other proteins are also typical of muscle—including titin (the largest known protein), a- and j3-actinin, desmin, and vimentin. 

Actin-binding proteins ABP-50, purification, 196, 78 ABP-120, purification, 196, 79 ABP-240 purification, 196, 76 effect on actin depolymerization, 215, 74 extraction, 196, 311 isolation from Dictyostelium discoideum, 196, 70 platelet-derived actin binding proteins [characterization, 215, 58 purification, 215, 58, 64 recombination with actin, 215, 73] 30-kDa Dictyostelium discoideum actin-crosslinking protein [assays, 196, 91 preparation, 196, 84] actin-depolymerizing factor [assay, 196, 132[ DNase assay, 196, 136 platelet-derived a-actinin [characterization, 215, 58 purification, 215, 58, 70 recombination with actin, 215, 73]. 

Other components, such as a-actinin and actin-related proteins (or ARPs), may also be recruited to the polymerization zone, whereas depolymerizing factors such as ADF and cofilin are apt to be selectively localized in the depolymerization zone. Note Agents that disrupt the formation of activated ABM clusters will also suppress the rate of assembly in the polymerization zone. See ABM-1 ABM-2 Sequences In Actin-Based Motors... 

Any of the cytoskeletal proteins that cross-link cytoskel-etal filaments into colinear arrays, such as the action of a-actinin in promoting the formation of actin stress fibers. Bundling proteins typically contain pairs of binding sites for attachment to cytoskeletal filaments. 

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... 

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