Disease relevance of TMOD1

• An improved Escherichia coli expression system for chicken E-tropomodulin was established and tropomodulin was prepared, Tmod (N39), in which 15 amino acid residues from the original C-terminus are deleted at the DNA level [1].

High impact information on TMOD1

• Requirement of pointed-end capping by tropomodulin to maintain actin filament length in embryonic chick cardiac myocytes [2].
• In striated muscle, it is believed that tight capping of the fast-growing (barbed) ends by CapZ and of the slow-growing (pointed) ends by tropomodulin (Tmod) stabilizes the uniform lengths of actin (thin) filaments in myofibrils [3].
• Here we have defined 1) the structural requirements of the N terminus of tropomyosin important for regulating the pointed end alone and with erythrocyte Tmod (Tmod1), and 2) the Tmod1 subdomains required for binding to tropomyosin and for regulating the pointed end [4].
• On the other hand, the actin-capping activity of the amino-terminal but not the carboxyl-terminal portion of Tmod1 is enhanced several thousand-fold in the presence of skeletal muscle tropomyosin [5].
• Tropomodulin assembles early in myofibrillogenesis in chick skeletal muscle: evidence that thin filaments rearrange to form striated myofibrils [6].

Biological context of TMOD1

• Competition studies using recombinant fragments of tropomodulin to map the binding domains for the two tropomyosins demonstrated that residues 6-94 contained the skeletal muscle tropomyosin binding site and residues 90-184 contained the erythrocyte tropomyosin binding site [7].
• Tmod was not detected in the undifferentiated epithelial cells but was expressed upon cell differentiation and assembled into F-actin and non-F-actin structures [8].

Anatomical context of TMOD1

• Tropomyosin-Tmod may function to locally regulate cytoskeletal dynamics in cells by stabilizing actin filaments [4].
• Isoform-specific interaction of tropomodulin with skeletal muscle and erythrocyte tropomyosins [7].
• Tropomodulin and tropomyosin mediate lens cell actin cytoskeleton reorganization in vitro [8].

Associations of TMOD1 with chemical compounds

• Tropomodulin has an unstructured N-terminal region that binds tropomyosin and a folded C-terminal domain with six leucine-rich repeats [9].
• Cross-linking experiments with glutaraldehyde indicated that Tmod (N39) and N11 can form complexes with tropomyosin, whereas C20 cannot [1].
• The model also suggests that interactions with tropomyosin, actin, and nebulin are all possible sources of influences on the dynamic properties of pointed-end capping by tropomodulin [10].

Analytical, diagnostic and therapeutic context of TMOD1

• NMR and circular dichroism were used to determine the structure of a peptide containing residues 1-92 of tropomodulin (Tmod1(1-92)) and to define its TM binding site [11].
• 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 [12].
• Tropomyosin and Tmod isoform expression was determined by immunoprecipitation and western blot analysis [8].
• Tmod isoforms expressed in the lens cell cultures were identical with those expressed in the embryonic chick lens fiber cells [8].
• Localization of F-actin, Tmod, and tropomyosin were determined by immunofluorescent staining followed by confocal microscopy [8].

References