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PMID:15469415

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Citation

Marco-Ferreres, R, Arredondo, JJ, Fraile, B and Cervera, M (2005) Overexpression of troponin T in Drosophila muscles causes a decrease in the levels of thin-filament proteins. Biochem. J. 386:145-52

Abstract

Formation of the contractile apparatus in muscle cells requires co-ordinated activation of several genes and the proper assembly of their products. To investigate the role of TnT (troponin T) in the mechanisms that control and co-ordinate thin-filament formation, we generated transgenic Drosophila lines that overexpress TnT in their indirect flight muscles. All flies that overexpress TnT were unable to fly, and the loss of thin filaments themselves was coupled with ultrastructural perturbations of the sarcomere. In contrast, thick filaments remained largely unaffected. Biochemical analysis of these lines revealed that the increase in TnT levels could be detected only during the early stages of adult muscle formation and was followed by a profound decrease in the amount of this protein as well as that of other thin-filament proteins such as tropomyosin, troponin I and actin. The decrease in thin-filament proteins is not only due to degradation but also due to a decrease in their synthesis, since accumulation of their mRNA transcripts was also severely diminished. This decrease in expression levels of the distinct thin-filament components led us to postulate that any change in the amount of TnT transcripts might trigger the down-regulation of other co-regulated thin-filament components. Taken together, these results suggest the existence of a mechanism that tightly co-ordinates the expression of thin-filament genes and controls the correct stoichiometry of these proteins. We propose that the high levels of unassembled protein might act as a sensor in this process.

Links

PubMed PMC1134776 Online version:10.1042/BJ20041240

Keywords

Actin Cytoskeleton/metabolism; Animals; Animals, Genetically Modified; Drosophila Proteins/biosynthesis; Drosophila Proteins/genetics; Drosophila Proteins/physiology; Drosophila melanogaster/growth & development; Drosophila melanogaster/metabolism; Drosophila melanogaster/ultrastructure; Feedback, Physiological; Flight, Animal; Gene Expression Regulation, Developmental/physiology; Muscle Proteins/biosynthesis; Muscles/metabolism; Muscles/ultrastructure; Muscular Diseases/etiology; Muscular Diseases/pathology; Pupa; RNA, Messenger/biosynthesis; Recombinant Fusion Proteins/biosynthesis; Recombinant Fusion Proteins/physiology; Sarcomeres/ultrastructure; Troponin T/biosynthesis; Troponin T/genetics; Troponin T/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:TNNT

involved_in

GO:0030239: myofibril assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:TNNT

involved_in

GO:0071689: muscle thin filament assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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