Disease relevance of Tm2

• A tropomyosin-2 mutation suppresses a troponin I myopathy in Drosophila [1].

Psychiatry related information on Tm2

• D53, a missense mutation, S185F, of the tropomyosin-2, Tm2, gene fully suppresses all the phenotypic effects of held-up(2), including the destructive hypercontraction of the indirect flight muscles (IFMs), a lack of jumping, the progressive myopathy of the walking muscles, and reductions in larval crawling and feeding behavior [1].

High impact information on Tm2

• The nucleotide sequence also establishes that two of the encoded proteins are tropomyosin isoforms, and two are related to tropomyosin [2].
• We find that haploidy of TmI causes myofibrillar disruptions and flightless behavior, but that haploidy of TmII causes neither [3].
• Single fiber mechanics demonstrates that power output is much lower in the TmI haploid line (32% of wild-type) than in the TmII haploid line (73% of wild-type) [3].
• These results indicate that head morphogenesis and the accumulation of high levels of oskar mRNA necessary for germ cell formation require tropomyosin-dependent cytoskeleton [4].
• One of these modifiers, Tm2, encodes tropomyosin, another component of the Tc-Tm complex [5].

Biological context of Tm2

• The S185F substitution in Tm2 is close to a troponin T binding site on tropomyosin [1].
• Interestingly, in Apis mellifera (hymenopteran), while most of the Tm1 and Tm2 gene features are conserved, the gene lacks any C-terminal exons [6].
• Dipteran genomes contain one tropomyosin gene that encodes one or two high-molecular weight isoforms (TmH) incorporating APPAEGA-rich sequences, specifically expressed in IFM [7].
• Vertebrate nonmuscle cells, such as human and rat fibroblasts, express multiple isoforms of tropomyosin, which are generated from four different genes and a combination of alternative promoter activities and alternative splicing [8].
• The differential expression of tropomyosin isoforms found in cell transformation and cell differentiation, as well as the differential localization of tropomyosin isoforms in some types of culture cells and developing neurons suggest a differential isoform function in vivo [8].

Anatomical context of Tm2

• Using a quantitative in vitro motility assay we have found that the wild type Drosophila ACT88F actin behaved like rabbit skeletal muscle actin when tropomyosin and troponin were added at pCa5 and pCa9 [9].
• The amount of GST-2 stably bound to the myofibril is directly proportional to the total amount of undigested TnH [10].
• The thorax RNAs encode a new tropomyosin isoform resolved on two-dimensional gels [11].
• The results of this analysis have allowed us to identify a region responsible for 20% of maximal TmI expression, estimate threshold levels of TmI RNA required for indirect flight and jump muscle function, and obtain evidence suggesting that sarcomere length may be an important determinant of flight muscle function [12].
• cDNA clones encoding two isoforms of chicken gizzard calponin, a recently identified actin- and tropomyosin-binding protein, have been isolated and sequenced [13].

Associations of Tm2 with chemical compounds

• Their N-termini are conventional and complete tropomyosin sequences, but their C-termini consist of different IFM-specific domains that are rich in proline, alanine, glycine and glutamate [6].
• The positions of tropomyosin in the mutant filaments, in both the Ca(2+)-free and the Ca(2+)-induced states, were the same, and identical to that of wild-type filaments in the presence of Ca(2+) [14].
• Aroclor 1254 and Cu(II) upregulated putative isoforms of tropomyosin and light chain of myosin [15].
• Two of these isoforms, which accumulated only in flight muscles, were unprecedented fusion proteins in which the tropomyosin sequence was joined to a carboxy-terminal proline-rich domain [16].
• OBJECTIVE: To investigate this cross-reactivity in vitro, we have taken advantage of a complementary DNA that expresses tropomyosin, the immunodominant shrimp allergen [17].

Physical interactions of Tm2

• The troponin was tightly bound to tropomyosin and could not be dissociated from it in non-denaturing conditions [18].

Regulatory relationships of Tm2

• A complex of Tn-T, Tn-H and tropomyosin inhibited actomyosin ATPase activity and the inhibition was relieved by Tn-C from vertebrate striated muscle in the presence of Ca2+ [18].
• We show that PDP1 is involved in regulating expression of the Tropomyosin I gene in somatic body-wall and pharyngeal muscles by binding to DNA sequences within the muscle activator that are required for activator function [19].
• Myocyte-specific enhancer factor 2 acts cooperatively with a muscle activator region to regulate Drosophila tropomyosin gene muscle expression [20].

Other interactions of Tm2

• Models to explain suppression by D53, derived from current knowledge of the vertebrate troponin-tropomyosin complex structure and functions, are discussed [1].
• Tn-H is easily digested by calpain, suggesting that part of the molecule has an extended configuration [18].
• The Drosophila sanpodo gene controls sibling cell fate and encodes a tropomodulin homolog, an actin/tropomyosin-associated protein [21].
• When embryos were glycerinated and then treated with tropomyosin before fixation, actin filaments were well visualized as thicker, uniform-sized filaments, though the number of filaments decreased probably owing to glycerination [22].
• A 21-residue peptide, obtained from endoproteinase Lys-C digested Pen a I by high-performance liquid chromatography, demonstrated significant homology (60-87%) with the muscle protein tropomyosin from various species and origins [23].

Analytical, diagnostic and therapeutic context of Tm2

• Complementary DNA clones coding for T. colubriformis muscle tropomyosin have been isolated and characterised as the first step in obtaining recombinant protein to carry out more extensive vaccination trials [24].
• We used a Drosophila melanogaster flightless mutant Ifm(3)3 and a genetic cross of this mutant with wild type flies to achieve a gradation of tropomyosin gene dosage [25].

References