title: Splice variants of enigma homolog, differentially expressed during heart development, promote or prevent hypertrophy.
abstract: OBJECTIVE
  Proteins with a PDZ (for PSD-95, DLG, ZO-1) and one to three LIM (for Lin11, Isl-1, Mec-3) domains are scaffolding sarcomeric and cytoskeletal elements that form structured muscle fibres and provide for the link to intracellular signalling by selectively associating protein kinases, ion channels, and transcription factors with the mechanical stress-strain sensors. Enigma homolog (ENH) is a PDZ-LIM protein with four splice variants: ENH1 with an N-terminal PDZ domain and three C-terminal LIM domains and ENH2, ENH3, and ENH4 without LIM domains. We addressed the functional role of ENH alternative splicing.
  
  
  RESULTS
  We studied the expression of the four ENH isoforms in the heart during development and in a mouse model of heart hypertrophy. All four isoforms are expressed in the heart but the pattern of expression is clearly different between embryonic, neonatal, and adult stages. ENH1 appears as the embryonic isoform, whereas ENH2, ENH3, and ENH4 are predominant in adult heart. Moreover, alternative splicing of ENH was changed following induction of heart hypertrophy, producing an ENH isoform pattern similar to that of neonatal heart. Next, we tested a possible causal role of ENH1 and ENH4 in the development of cardiac hypertrophy. When overexpressed in rat neonatal cardiomyocytes, ENH1 promoted the expression of hypertrophy markers and increased cell volume, whereas, on the contrary, ENH4 overexpression prevented these changes.
  
  
  CONCLUSIONS
  Antagonistic splice variants of ENH may play a central role in the adaptive changes of the link between mechanical stress-sensing and signalling occurring during embryonic development and/or heart hypertrophy.
authors.affiliation: Fondation pour Recherches Médicales, Medical Faculty, University of Geneva, Geneva 1211, Switzerland.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Sébastien
authors.initials: S
authors.lastname: Wälchli
authors.forename: Toshitsugu
authors.initials: T
authors.lastname: Fujita
authors.forename: Stephan
authors.initials: S
authors.lastname: Ryser
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hoshijima
authors.forename: Werner
authors.initials: W
authors.lastname: Schlegel
authors.forename: Shun'ichi
authors.initials: S
authors.lastname: Kuroda
authors.forename: Andrés D
authors.initials: AD
authors.lastname: Maturana
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D048429:Cell Size; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D054731:PDZ Domains; D020033:Protein Isoforms; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C510085:ENH protein, mouse; D008840:Microfilament Proteins; C102578:Pdlim5 protein, rat; D020033:Protein Isoforms