Disease relevance of wupA

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

High impact information on wupA

• The specificity of mutant phenotypes suggests a functional role of particular TnI isoforms in the development and the mature activity of muscle and nervous systems [2].
• Troponin I is encoded in the haplolethal region of the Shaker gene complex of Drosophila [2].
• Specific myosin heavy chain mutations suppress troponin I defects in Drosophila muscles [3].
• We find that the heldup gene encodes troponin-I, one of the principal regulatory proteins associated with skeletal muscle thin filaments. heldup3, heldup4, and heldup5 mutants, all of which have grossly abnormal flight muscle myofibrils, lack mRNAs encoding one or more troponin-I isoforms [4].
• By sequencing mutant troponin-I cDNAs we demonstrate that the molecular basis for muscle degeneration in heldup2 is conversion of an invariant alanine residue to valine [4].

Biological context of wupA

• A suppressor mutation, D53, of the held-up(2) allele of the Drosophila melanogaster Troponin I (wupA) gene is described [1].
• TnI is part of the thin filament troponin complex which regulates muscle contraction [5].
• Troponin I is required for myofibrillogenesis and sarcomere formation in Drosophila flight muscle [5].
• We have tested the hypothesis that missense mutations of the myosin heavy chain gene, Mhc, which suppress the hypercontraction of the TnI mutant held-up(2) (hdp(2)), do so by reducing actomyosin force production [6].
• The troponin I (TnI) gene of Drosophila melanogaster encodes a family of 10 isoforms resulting from the differential splicing of 13 exons [7].

Anatomical context of wupA

• A troponin I (TnI) mutation, hdp(3), leads to an absence of TnI in the IFMs and tergal depressor of trochanter (TDT) muscles due to a transcript-splicing defect [5].
• Electron micrographs of negatively stained specimens showed that Lethocerus thin filaments have projections at about 39 nm intervals, which are not seen on thin filaments from vertebrate striated muscle and are probably due to the relatively large troponin complex [8].
• Muscles endowed with TnI mutated at both sites support nearly normal myofibrillar structure, perform notably well in wing beating and flight tests, and isolated muscle fibers produce active force [9].
• Calcineurin function is required for myofilament formation and troponin I isoform transition in Drosophila indirect flight muscle [10].
• The aim of this paper was to study the presence and distribution of troponin in different muscle cell types from the earthworm Eisenia foetida (the muscular body wall, and the inner and outer muscular layer of the pseudoheart) [11].

Associations of wupA with chemical compounds

• The myosin heavy and light chain genes, the actin genes, the troponin genes, and the atrial natriuretic factor and muscle creatine kinase genes have served as excellent paradigms for the study of cardiac gene expression [12].
• The second site suppression is due to a leucine to phenylalanine change within a heptameric leucine string motif adjacent to the actin binding domain of TnI [9].
• To investigate this possibility further, thin filaments were isolated from troponin-regulated, indirect flight muscles of Drosophila mutants that express actin with an amino acid charge reversal at residue 93 located at the interface between actin subdomains 1 and 2, in which a lysine residue is substituted for a glutamic acid [13].

Physical interactions of wupA

• The troponin was tightly bound to tropomyosin and could not be dissociated from it in non-denaturing conditions [8].

Other interactions of wupA

• Models to explain suppression by D53, derived from current knowledge of the vertebrate troponin-tropomyosin complex structure and functions, are discussed [1].
• Flight muscle contraction is regulated by both stretch and Ca(2+)-induced thin filament (actin + tropomyosin + troponin complex) activation [6].
• Decoration of the thin filaments with myosin subfragment-1 in rigor conditions appeared not to be affected by the troponin [8].
• Since then, only two haplolethals, 22F1-2 and 16F, have been directly linked to identified genes, dpp and wupA, respectively [14].
• This mechanism is not exclusive to the Troponin T gene, but is also relevant to the muscle-specific Troponin I gene [15].

Analytical, diagnostic and therapeutic context of wupA

• Immunocytochemical electron microscopic study and Western blot analysis of troponin in striated muscle of the fruit fly Drosophila melanogaster and in several muscle cell types of the earthworm Eisenia foetida [11].
• The use of such antisera in the labeling of Drosophila salivary gland chromosomes by indirect immunofluorescence shows concentrations of immunoreactive HDP in many regions, but especially in chromosome puffs [16].

References