Tropomyosin‐troponin complex stabilizes the pointed ends of actin filaments against polymerization and depolymerization

Weigt, Christiane; Schoepper, Beate; Wegner, Albrecht

doi:10.1016/0014-5793(90)80119-4

Cited by 42 publications

(26 citation statements)

References 17 publications

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“…The specification of thin filament length in striated muscle is likely to require multiple interacting components. Tropomyosin, for example, has been shown in in vitro assays to reduce actin filament depolymerization at pointed ends (Broschat, 1990;Weigt et al, 1990) and has been proposed to function in thin filament length determination through a vernier-like mechanism (Huxley and Brown, 1967). Since tropomodulin binds to one end of tropomyosin (Fowler, 1990), it appears likely that together, tropomyosin and tropomodulin function to maintain and stabilize actin filament length at the pointed ends of the thin filaments.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of thin filament assembly in embryonic chick cardiac myocytes: tropomodulin requires tropomyosin for assembly.

Gregorio

Fowler

1995

The Journal of Cell Biology

100

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Abstract. Tropomodulin is a pointed end capping protein for tropomyosin-coated actin filaments that is hypothesized to play a role in regulating the precise lengths of striated muscle thin filaments (Fowler, V. M., M. A. Sussman, P. G. Miller, B. E. Flucher, and M. P. Daniels. 1993. J. Cell Biol. 120:411-420;Weber, A., C. C. Pennise, G. G. Babcock, and V. M. Fowler. 1994. J. Cell Biol. 127:1627-1635. To gain insight into the mechanisms of thin filament assembly and the role of tropomodulin therein, we have characterized the temporal appearance, biosynthesis and mechanisms of assembly of tropomodulin onto the pointed ends of thin filaments during the formation of striated myofibrils in primary embryonic chick cardiomyocyte cultures. Our results demonstrate that tropomodulin is not assembled coordinately with other thin filament proteins. Double immunofluorescence staining and ultrastructural immunolocalization demonstrate that tropomodulin is incorporated in its characteristic sarcomeric location at the pointed ends of the thin filaments after the thin filaments have become organized into periodic I bands. In fact, tropomodulin assembles later than all other well characterized myofibrillar proteins studied including: actin, tropomyosin, ~actinin, titin, myosin and C-protein. Nevertheless, at steady state, a significant proportion (,,o39%) of tropomodulin is present in a soluble pool throughout myofibril assembly. Thus, the absence of tropomodulin in some striated myofibrils is not due to limiting quantities of the protein. In addition, kinetic data obtained from [35S]methionine pulse-chase experiments indicate that tropomodulin assembles more slowly into myofibrils than does tropomyosin. This observation, together with results obtained using a novel permeabilized cell model for thin filament assembly, indicate that tropomodulin assembly is dependent on the prior association of tropomyosin with actin illaments. We conclude that tropomodulin is a late marker for the assembly of striated myofibrils in cardiomyocytes; its assembly appears to be linked to their maturity, We propose that tropomodulin is involved in maintaining and stabilizing the final lengths of thin filaments after they are assembled.SEMBLV of myofibrils during striated muscle differentiation is a complex process that requires coordinate expression of the constituent proteins and their association into highly organized sarcomeres. Multiple proteins appear to be responsible for specifically regulating the length, polarity, stability and spatial organization of thin filaments during myofibrillogenesis: properties which are required for efficient contraction. Proteins associated with the barbed (fast-growing) ends of muscle thin filaments at the Z disk assemble early during myofibrillogenesis; for example, the actin filament barbed end capping protein, capZ and the actin cross-linking protein, c¢-actinin (for example, see Sanger et al., 1986;Schultheiss et al., 1990;Schafer et al.,

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Section: Discussionmentioning

confidence: 99%

Mechanisms of thin filament assembly in embryonic chick cardiac myocytes: tropomodulin requires tropomyosin for assembly.

Gregorio

Fowler

1995

The Journal of Cell Biology

100

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“…Tropomyosin not only directly prevents actin depolymerization in vitro by binding in a head-totail arrangement along the actin filament, but also reduces the depolymerization affects of DNaseI and ADF/cofilin, and severing by gelsolin (Bernstein and Bamburg, 1982;Broschat, 1990;Fattoum et al, 1983;Hitchcock et al, 1976;Weigt et al, 1990). The stabilizing activity of tropomyosin has also been shown in vivo, because a reduction of tropomyosin levels results in disorganized thin filaments in the body wall muscles of Caenorhabditis elegans (Ono and Ono, 2002).…”

Section: Introductionmentioning

confidence: 99%

Leiomodin-2 is an antagonist of tropomodulin-1 at the pointed end of the thin filaments in cardiac muscle

Tsukada

Pappas

Moroz

et al. 2010

Journal of Cell Science

202

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SummaryRegulation of actin filament assembly is essential for efficient contractile activity in striated muscle. Leiomodin is an actin-binding protein and homolog of the pointed-end capping protein, tropomodulin. These proteins are structurally similar, sharing a common domain organization that includes two actin-binding sites. Leiomodin also contains a unique C-terminal extension that has a third actinbinding WH2 domain. Recently, the striated-muscle-specific isoform of leiomodin (Lmod2) was reported to be an actin nucleator in cardiomyocytes. Here, we have identified a function of Lmod2 in the regulation of thin filament lengths. We show that Lmod2 localizes to the pointed ends of thin filaments, where it competes for binding with tropomodulin-1 (Tmod1). Overexpression of Lmod2 results in loss of Tmod1 assembly and elongation of the thin filaments from their pointed ends. The Lmod2 WH2 domain is required for lengthening because its removal results in a molecule that caps the pointed ends similarly to Tmod1. Furthermore, Lmod2 transcripts are first detected in the heart after it has begun to beat, suggesting that the primary function of Lmod2 is to maintain thin filament lengths in the mature heart. Thus, Lmod2 antagonizes the function of Tmod1, and together, these molecules might fine-tune thin filament lengths.

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“…However, the interaction ofactin with other proteins, such as the tropomyosins and troponins, must be important for thin filament assembly. Tropomyosin has been implicated in stabilizing F-actin in vivo [187,188]. The myofibrils of the Act88F mutant E93K have thin filaments but no Z-discs and it has been proposed that this mutant may reduce binding of a Z-disc protein, perhaps ac-actinin [22].…”

Section: Studies In Vivo Cell Biologymentioning

confidence: 99%

Molecular genetics of actin function

Hennessey

Drummond

Sparrow

1993

Biochemical Journal

103

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Tropomyosin‐troponin complex stabilizes the pointed ends of actin filaments against polymerization and depolymerization

Cited by 42 publications

References 17 publications

Mechanisms of thin filament assembly in embryonic chick cardiac myocytes: tropomodulin requires tropomyosin for assembly.

Mechanisms of thin filament assembly in embryonic chick cardiac myocytes: tropomodulin requires tropomyosin for assembly.

Leiomodin-2 is an antagonist of tropomodulin-1 at the pointed end of the thin filaments in cardiac muscle

Molecular genetics of actin function

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