Connectin/titin, giant elastic protein of muscle

Maruyama, Kosçak

doi:10.1096/fasebj.11.5.9141500

Cited by 225 publications

(124 citation statements)

References 34 publications

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“…For example, in tendon cells subjected to cyclic stretching of 5% strain at 1 Hz for 6 h in vitro, expression of collagen type I was increased at the transcriptional level, as was the expression of several other genes including connectin, cystatin, and calmodulin (Banes et al, 1999). Connectin is an elastic protein whose role may be as a shock cord to keep sarcomeres from pulling apart (Maruyama, 1997). Its presence in tendon could serve to prevent cell syncytia from pulling apart under dynamic loads.…”

Section: Regulation Of Gene Expression In Fibroblasts By Mechanical Lmentioning

confidence: 99%

Mechanoregulation of gene expression in fibroblasts

Wang

Thampatty

Lin

et al. 2007

Gene

225

187

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Mechanical loads placed on connective tissues alter gene expression in fibroblasts through mechanotransduction mechanisms by which cells convert mechanical signals into cellular biological events, such as gene expression of extracellular matrix components (e.g., collagen). This mechanical regulation of ECM gene expression affords maintenance of connective tissue homeostasis. However, mechanical loads can also interfere with homeostatic cellular gene expression and consequently cause the pathogenesis of connective tissue diseases such as tendinopathy and osteoarthritis. Therefore, the regulation of gene expression by mechanical loads is closely related to connective tissue physiology and pathology. This article reviews the effects of various mechanical loading conditions on gene regulation in fibroblasts and discusses several mechanotransduction mechanisms. Future research directions in mechanoregulation of gene expression are also suggested.

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Section: Regulation Of Gene Expression In Fibroblasts By Mechanical Lmentioning

confidence: 99%

Mechanoregulation of gene expression in fibroblasts

Wang

Thampatty

Lin

et al. 2007

Gene

225

187

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“…Kettin is one of the first proteins to colocalize with actin during the early stages of myofibrillogenesis (Ayme-Southgate et al, 2004), and genetic analysis has shown that it is essential for myofibril assembly in the fruit fly (Hakeda et al, 2000). The sequence of kettin contains 35 immunoglobulin-like (Ig) repeats separated by short linker sequences (Hakeda et al, 2000;Kolmerer et al, 2000) and is related to the connectin/titin family of giant elastic proteins (Maruyama, 1997;Gautel et al, 1999;Gregorio et al, 1999;Maruyama and Kimura, 2000;Granzier et al, 2002). However, kettin does not have fibronectin-like, elastic PEVK, or kinase domains, and seems to be a uniquely evolved member of the connectin/titin family of proteins.…”

Section: Introductionmentioning

confidence: 99%

Caenorhabditis elegansKettin, a Large Immunoglobulin-like Repeat Protein, Binds to Filamentous Actin and Provides Mechanical Stability to the Contractile Apparatuses in Body Wall Muscle

Ono

Mohri

et al. 2006

MBoC

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Kettin is a large actin-binding protein with immunoglobulin-like (Ig) repeats, which is associated with the thin filaments in arthropod muscles. Here, we report identification and functional characterization of kettin in the nematode Caenorhabditis elegans. We found that one of the monoclonal antibodies that were raised against C. elegans muscle proteins specifically reacts with kettin (Ce-kettin). We determined the entire cDNA sequence of Ce-kettin that encodes a protein of 472 kDa with 31 Ig repeats. Arthropod kettins are splice variants of much larger connectin/titin-related proteins. However, the gene for Ce-kettin is independent of other connectin/titin-related genes. Ce-kettin localizes to the thin filaments near the dense bodies in both striated and nonstriated muscles. The C-terminal four Ig repeats and the adjacent non-Ig region synergistically bind to actin filaments in vitro. RNA interference of Ce-kettin caused weak disorganization of the actin filaments in body wall muscle. This phenotype was suppressed by inhibiting muscle contraction by a myosin mutation, but it was enhanced by tetramisole-induced hypercontraction. Furthermore, Ce-kettin was involved in organizing the cytoplasmic portion of the dense bodies in cooperation with ␣-actinin. These results suggest that kettin is an important regulator of myofibrillar organization and provides mechanical stability to the myofibrils during contraction. INTRODUCTIONIn muscle cells, the actin cytoskeleton is highly differentiated to form the myofibrils that are specialized for producing contractile forces. In addition to actin and myosin as the essential contractile components, regulatory components for the contractile activity are integrated into the structure (Squire, 1997). Despite the fact that many myofibrillar components have been identified, little is known about how these components functionally interact to assemble and maintain the myofibrils in living cells (Littlefield and Fowler, 1998;Gregorio and Antin, 2000;Clark et al., 2002). In particular, the assembly process of actin filaments is complex. During development, actin-monomer binding proteins, including profilin, and actin depolymerizing factor/cofilin regulate actin filament dynamics (Obinata, 1993;Obinata et al., 1997; Ono, 2003a,b). However, in mature myofibrils, these proteins are no longer major components of the thin filaments, and filament binding proteins, such as tropomyosin and ␣-actinin, and end-capping proteins, such as CapZ and tropomodulin, become the major actin-associated proteins. However, the list of actin binding proteins in muscle is still growing and cellular functions of many of these proteins are not clearly understood.Kettin is a large protein of 500-700 kDa found in the Z-discs and the I-bands of arthropod muscles (Bullard et al., 2000;Bullard et al., 2002Bullard et al., , 2006. Kettin directly binds to actin filaments with high-affinity (Lakey et al., 1993;Maki et al., 1995;van Straaten et al., 1999). Proteolytic removal of kettin by calpain from the Z-discs causes ...

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“…T itins are 3.0-3.7 MDa filamentous proteins extending between the Z-and M-lines of the sarcomere (1)(2)(3)(4). Titin is a tandem array of Ig type C2 and fibronectin (FN) type III domains (Ϸ300 per molecule) interspersed with unique sequences, most notably the Pro-, Glu-, Val-, and Lys-rich PEVK segment, and the N2A and N2B segments (5).…”

mentioning

confidence: 99%

Global configuration of single titin molecules observed through chain-associated rhodamine dimers

Grama

Somogyi

Kellermayer

2001

Proc. Natl. Acad. Sci. U.S.A.

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The global configuration of individual, surface-adsorbed molecules of the giant muscle protein titin, labeled with rhodamine conjugates, was followed with confocal microscopy. Fluorescence-emission intensity was reduced because of self-quenching caused by the close spacing between rhodamine dye molecules that formed dimers. In the presence of chemical denaturants, fluorescence intensity increased, reversibly, up to 5-fold in a fast reaction; the kinetics were followed at the single-molecule level. We show that dimers formed in a concentrated rhodamine solution dissociate when exposed to chemical denaturants. Furthermore, titin denaturation, followed by means of tryptophan fluorescence, is dominated by a slow reaction. Therefore, the rapid fluorescence change of the single molecules reflects the direct action of the denaturants on rhodamine dimers rather than the unfolding͞refolding of the protein. Upon acidic denaturation, which we have shown not to dissociate rhodamine dimers, fluorescence intensity change was minimal, suggesting that dimers persist because the unfolded molecule has contracted into a small volume. The highly contractile nature of the acid-unfolded protein molecule derives from a significant increase in chain flexibility. We discuss the potential implications this finding could have for the passive mechanical behavior of striated muscle.T itins are 3.0-3.7 MDa filamentous proteins extending between the Z-and M-lines of the sarcomere (1-4). Titin is a tandem array of Ig type C2 and fibronectin (FN) type III domains (Ϸ300 per molecule) interspersed with unique sequences, most notably the Pro-, Glu-, Val-, and Lys-rich PEVK segment, and the N2A and N2B segments (5). The I-band segment of titin acts as a molecular spring, whose elastic properties define the passive or restoring mechanical properties of striated muscle (6-9). By contrast, titin's A-band segment is thought to function as a scaffold that defines structural regularity within the A band (10). Recent single-molecule experiments often have used titin as a model system because of a large size that makes it relatively easily accessible to such investigations. Single-molecule-mechanics experiments using either optical tweezers (11-13) or atomic force microscopy (AFM; ref. 14) described titin as an entropic chain in which domain unfolding occurs at high forces and refolding occurs at low forces. These experiments formed the basis of many theoretical and modeling works that addressed the mechanisms of mechanically driven protein folding (15)(16)(17)(18)(19)(20). Individual titin molecules can be made visible under aqueous conditions after labeling with fluorophores. Fluorescently labeled titin molecules have recently been studied under various conditions: equilibration to a surface (21-23), stretching with meniscus force (22, 23) and direct manipulation (24), and chemical denaturation (25,26). Chemical denaturation has been shown to cause an abrupt and significant rise in the fluorescence intensity of Oregon Green 488 (Molecular Probes) maleimi...

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Connectin/titin, giant elastic protein of muscle

Cited by 225 publications

References 34 publications

Mechanoregulation of gene expression in fibroblasts

Mechanoregulation of gene expression in fibroblasts

Caenorhabditis elegansKettin, a Large Immunoglobulin-like Repeat Protein, Binds to Filamentous Actin and Provides Mechanical Stability to the Contractile Apparatuses in Body Wall Muscle

Global configuration of single titin molecules observed through chain-associated rhodamine dimers

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