Differential Muscle-type Expression of the Drosophila Troponin T Gene

Abstract

The complete genomic organization of the Drosophila troponin T (TnT) gene shows many interesting features, including the presence of a microexon of only 3 nucleotides conserved among Drosophilidae. It is the smallestbona fide exon so far described, placing a new lower limit on the nucleotide number required for correct splicing. Four muscle-type specific transcripts are generated by developmentally regulated alternative splicing. Exons 3, 4, and 5 are absent in the transcript present in jump and flight muscles. A total of 11 exons are present in the adult hypodermic muscles transcript, whereas the microexon is absent in the larval hypodermic musculature. The two isoforms differ in a lysine residue. Post-translational regulation of the flight muscles/tergal depressor of the trochanter-specific isoform is involved in flight and/or jump function. The interaction domains of TnT in the tropomyosin-troponin complex are strongly conserved in the known vertebrate and invertebrate TnT sequences, whereas the terminal regions show an important variability. The COOH-terminal region shows important phylogenetic variations, whereas the NH2-terminal domain is associated with specific muscle types in a particular organism, a finding that discloses a selective value for these domains in the functionality of distinct muscles in different organisms. The complete genomic organization of the Drosophila troponin T (TnT) gene shows many interesting features, including the presence of a microexon of only 3 nucleotides conserved among Drosophilidae. It is the smallestbona fide exon so far described, placing a new lower limit on the nucleotide number required for correct splicing. Four muscle-type specific transcripts are generated by developmentally regulated alternative splicing. Exons 3, 4, and 5 are absent in the transcript present in jump and flight muscles. A total of 11 exons are present in the adult hypodermic muscles transcript, whereas the microexon is absent in the larval hypodermic musculature. The two isoforms differ in a lysine residue. Post-translational regulation of the flight muscles/tergal depressor of the trochanter-specific isoform is involved in flight and/or jump function. The interaction domains of TnT in the tropomyosin-troponin complex are strongly conserved in the known vertebrate and invertebrate TnT sequences, whereas the terminal regions show an important variability. The COOH-terminal region shows important phylogenetic variations, whereas the NH2-terminal domain is associated with specific muscle types in a particular organism, a finding that discloses a selective value for these domains in the functionality of distinct muscles in different organisms. Much of our understanding of the regulation of muscle contraction derives from studies of vertebrate skeletal muscle. The process is controlled by the reversible binding of Ca2+ to the thin filament protein troponin (1Ishii Y. Lehrer S.S. J. Biol. Chem. 1991; 266: 6894-6903Abstract Full Text PDF PubMed Google Scholar, 2Lehman W. Craig R. Vibert P. Nature. 1994; 368: 65-67Crossref PubMed Scopus (275) Google Scholar). Although there are differences in the known details of this process in different muscles, the basic process is similar (1Ishii Y. Lehrer S.S. J. Biol. Chem. 1991; 266: 6894-6903Abstract Full Text PDF PubMed Google Scholar, 2Lehman W. Craig R. Vibert P. Nature. 1994; 368: 65-67Crossref PubMed Scopus (275) Google Scholar, 3Ruegg J.C. Calcium in Muscle Contraction. Springer-Verlag-Heidelberg, Berlin1992Crossref Google Scholar). The detailed structure and protein domains involved in the formation of the tropomyosin-troponin complex, and hence the details of how it functions, are not known (3Ruegg J.C. Calcium in Muscle Contraction. Springer-Verlag-Heidelberg, Berlin1992Crossref Google Scholar). The role of the highly asymmetric TnT 1The abbreviations used are: TnT, troponin T; TDT, tergal depressor of the trochanter; IFM, indirect flight muscles; bp, base pair(s); kb, kilobase(s); RT, reverse transcriptase; PCR, polymerase chain reaction. protein in the regulatory mechanism of muscle contraction is still unclear, but previous reports in vertebrate muscles indicate that it is a key component in linking together and regulating all the components of the complex, i.e. tropomyosin, troponin I, and troponin C (4Ohtsuki I. Nagano K. Adv. Biophys. 1982; 15: 93-130Crossref PubMed Scopus (27) Google Scholar, 5Fisher D. Wang G. Tobacman L.S. J. Biol. Chem. 1995; 270: 25455-25460Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 6Potter J.D. Sheng Z. Pan B.S. Zhao J. J. Biol. Chem. 1995; 270: 2557-2562Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar). In addition, it increases the cooperativity of actin-tropomyosin and provides Ca2+ sensitivity to the thin filament (7Schaertl S Lehrer S.S. Geeves M.A. Biochemistry. 1995; 34: 15890-15894Crossref PubMed Scopus (110) Google Scholar). TnT is one of the proteins known to present a very complex isoform pattern both at the transcript level through differential splicing and at the protein level through post-translational modification (8Schiaffino S. Reggiani C. Physiol. Rev. 1996; 76: 371-423Crossref PubMed Scopus (1271) Google Scholar). Furthermore, mutations in cardiac TnT are responsible for a large proportion of familial hypertrophic cardiomyopathy cases (9Watkins H. McKenna W.J. Thierfelder L. Suk H.J. Anan R. O'Donoghue A. Spirito P. Matsumori A. 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J. J. C. R. J. Muscle Res. Cell Google the expression of this region more distinct In this an exon a and two different reverse The the of the of exon 11 and the of the including the the 5 The complete analysis of the revealed that TnT transcripts only alternative splicing in the region the The muscle of these transcripts in of muscles with TDT, IFM, muscles from and larval hypodermic muscles alternative splicing been only in the of TnT, the on this and of the revealed that transcripts in a The transcript present in and flight muscles not exons 3, 4, and 5 and is in 5 muscles show two distinct In the adult hypodermic muscles, the 11 exons of the gene whereas in the larval hypodermic the microexon The hypodermic transcripts differ only in the In muscles from the transcript is in larval hypodermic muscles; that the microexon is the transcript not exons and 5 in This transcript to the in and larval and not been to a particular muscle This transcript is present in in and larval than in adult present different muscles and the transcripts present in hypodermic and muscles have been it is possible that this transcript in heart the muscle of of these two distinct for in the exon a to both and adult and present in all muscles A and The exons 3 and 5 to both the and adult but absent in the and muscles and The transcript that exon and 5 the to these exons are 3 and in In the present revealed that the TnT gene transcripts specific to different muscle and and and of by a Drosophila TnT in embryonic and larval A. 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TnT gene for In this one that Drosophila two distinct of muscles and adult with different muscles are muscles responsible for larval The hypodermic in the in microexon is and with the and muscles in and Rev. PubMed Scopus Google Scholar, D. R. J. Cell Biol. 1996; PubMed Scopus Google Scholar). exon a very exon for only to Drosophila muscle It of interest to that there is an important in the region of the is in the cardiac The regions of are and similar to Drosophila and the the domain is similar in to the vertebrate skeletal muscle to the splicing in the a present in is not in of the invertebrate so far 1994; PubMed Scopus Google Scholar). is to this an of the TnT is through this region and domains of the TnT Biochemistry. 1996; PubMed Scopus Google Scholar). The is different in the of the COOH-terminal region of This region important but is not by an alternative splicing The only in vertebrate skeletal muscle TnT, in two and have been in this the known TnT protein are (8Schiaffino S. 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The of a C. elegans this (12Myers C.D. Goh P.-Y. Allen T. Bucher E.A. Bogaert T J. Cell Biol. 1996; 132: 1061-1077Crossref PubMed Scopus (86) Google that at the show a muscle that muscle contraction Muscle in this mutant In of thin and to but in they not to assembly is defective it is (12Myers C.D. Goh P.-Y. Allen T. Bucher E.A. Bogaert T J. Cell Biol. 1996; 132: 1061-1077Crossref PubMed Scopus (86) Google Scholar). A TnT mutant in Drosophila, a the COOH-terminal (11Fyrberg E. Fyrberg C.C. Beall C. Saville D.L. J. Mol. Biol. 1990; 216: 657-675Crossref PubMed Scopus (95) Google Scholar). have TnT in flight muscles and thin the are It that the role of TnT in the invertebrate troponin complex regulating muscle contraction is different and more complex than in in the TnT interaction domains with with and have been in two different regions in in the and to the of the vertebrate protein (4Ohtsuki I. Nagano K. Adv. 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Chem. 1991; 266: Full Text PDF PubMed Google Scholar) have been in all the invertebrate known in strongly that post-translational TnT protein to a more basic than the a more level of regulation in the of more specific muscle in a is the of the flight jump of the muscles The of of these been in vertebrate but is still with is a very to the functionality of this isoform variability. R. and A. for of the