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A novel protein involved in heart development in Ambystoma mexicanum is localized in endoplasmic reticulum

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Journal of Biomedical Science

Abstract

The discovery of the naturally occurring cardiac non-function (c) animal strain in Ambystoma mexicanum (axolotl) provides a valuable animal model to study cardiomyocyte differentiation. In homozygous mutant animals (c/c), rhythmic contractions of the embryonic heart are absent due to a lack of organized myofibrils. We have previously cloned a partial sequence of a peptide cDNA (N1) from an anterior-endoderm-conditioned-medium RNA library that had been shown to be able to rescue the mutant phenotype. In the current studies we have fully cloned the N1 full length cDNA sequence from the library. N1 protein has been detected in both adult heart and skeletal muscle but not in any other adult tissues. GFP-tagged expression of the N1 protein has revealed localization of the N1 protein in the endoplasmic reticulum (ER). Results from in situ hybridization experiments have confirmed the dramatic decrease of expression of N1 mRNA in mutant (c/c) embryos indicating that the N1 gene is involved in heart development.

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References

  1. Hoffman JIE, Kaplan S (2002) The incidence of congenital heart disease. J Am Coll Cardiol 39:1890–1900

    Article  PubMed  Google Scholar 

  2. McKenna WJ (2008) Genetics of hypertrophic cardiomyopathy. In: UpToDate. Rose BD (ed) UpToDate, Waltham, MA

  3. Kamisago M, Sharma DS, DePalma SR, Solomon S, Sharma P, McDonough B, Smoot L, Mullen MP, Woolf PK, Wigle ED, Seidman JG, Seidman CE (2000) Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy. N Engl J Med 343:1688–1696

    Article  PubMed  CAS  Google Scholar 

  4. Humphrey RR (1972) Genetic and experimental studies on a mutant gene (c) determining absence of heart action in embrios of the Mexican Axolotl (Ambystoma mexicanum). Dev Biol 27:365–375

    Article  PubMed  CAS  Google Scholar 

  5. Lemanski LF (1973) Morphology of developing heart in cardiac lethal mutant Mexican Axolotls, Ambystoma Mexicanum. Dev Biol 33:312–333

    Article  PubMed  CAS  Google Scholar 

  6. LaFrance SM, Lemanski LF (1994) Imunofluorescent confocal analysis of tropomyosin in developing hearts of normal and cardiac mutant axolotls. Int J Devel Biol 38:695–700

    CAS  Google Scholar 

  7. Jacobson AG, Duncan JT (1968) Heart induction in salamanders. J Exp Zool 167:79–104

    Article  PubMed  CAS  Google Scholar 

  8. Jacobson AG, Sater AK (1988) Features of embryonic induction. Development 104:341–359

    PubMed  CAS  Google Scholar 

  9. Lemanski LF, Paulson DJ, Hill CS (1979) Normal anterior endoderm corrects heart defect in cardiac mutant salamanders (Ambystoma Mexicanum). Science 204:860–862

    Article  PubMed  CAS  Google Scholar 

  10. Davis LA, Lemanski LF (1987) Induction of myofibrillogenesis in cardiac lethal mutant axolotl hearts rescued by RNA derived from normal endoderm. Development 99:145–154

    PubMed  CAS  Google Scholar 

  11. Lemanski LF, Nakatsugawa M, Bhatia R, Erginel-Unaltuna N, Spinner BJ, Dube DK (1996) A specific synthetic RNA promotes cardiac myofibrillogenesis in the Mexican axolotl. Biochem Biophys Res Com 229:974–981

    Article  PubMed  CAS  Google Scholar 

  12. Erginel-Unaltuna N, Dube DK, Salsbury KG, Lemanski LF (1995) Confocal microscopy of a newly identified protein associated with heart development in the Mexican axoltl. Cell Mol Biol Re 41:117–130

    CAS  Google Scholar 

  13. Zhang C, Meng F, Huang XP, Zajdel R, Lemanski SL, Foster D, Erginel-Unaltuna N, Dube DK, Lemanski LF (2004) Downregulation of N1 gene expression inhibits the initial heartbeating and heart development in axolotls. Tissue Cell 36:71–81

    Article  PubMed  CAS  Google Scholar 

  14. Zajdel RW, McLean MD, Lemanski SL, Muthuchamy M, Wieczorek DF, Lemanski LF, Dube DK (1998) Ectopic expression of tropomyosin promotes myofibrillogenesis in mutant axolotl hearts. Dev Dyn 213:412–420

    Article  PubMed  CAS  Google Scholar 

  15. Duvernay MT, Zhou F, Wu G (2004) Conserved motif for the transport of G protein-coupled receptors from the endoplasmic reticulum to the cell surface. J Biol Chem 279:30741–30750

    Article  PubMed  CAS  Google Scholar 

  16. Zhang C, Dube DK, Huang X, Zajdel RW, Bhatia R, Foster D, Lemanski SL, Lemanski LF (2003) A point mutation in bioactive RNA results in the failure of mutant heart correction in Mexican axolotls. Anat Embryol 206:495–506

    PubMed  CAS  Google Scholar 

  17. Srivastava D, Olson EN (2000) A genetic blueprint for cardiac development. Nature 407:221–226

    Article  PubMed  CAS  Google Scholar 

  18. Olson EN (2006) Gene regulatory networks in the evolution and development of the heart. Science 313:1922–1927

    Article  PubMed  CAS  Google Scholar 

  19. LaFrance SM, Fransen ME, Erginel-Unaltuna N, Dube DK, Robertson DR, Stefanu C, Ray TK, Lemanski LF (1993) RNA from normal anterior endoderm/mesoderm-conditioned medium stimulates myofibrillogenesis in developing mutant axolotl hearts. Cell Mol Biol Res 39:547–560

    PubMed  CAS  Google Scholar 

  20. Munro S, Pelham HR (1987) C-terminal signal prevents secretion of luminal ER proteins. Cell 48:899–907

    Article  PubMed  CAS  Google Scholar 

  21. Jackson MR, Nilsson T, Peterson PA (1990) Identification of a consensus motif for retention of transmembrane proteins in the endoplasmic reticulum. EMBO J 9:3153–3162

    PubMed  CAS  Google Scholar 

  22. Zerangue N, Schwappach B, Jan YN, Jan LY (1999) A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels. Neuron 22:537–548

    Article  PubMed  CAS  Google Scholar 

  23. Xie R, Clark KM, Gorovsky MA (2007) Endoplasmic reticulum retention signal-dependent glycylation of the Hsp70/Grp170-related Pgp1p in Tetrahymena. Eukaryot Cell 6:388–397

    Article  PubMed  CAS  Google Scholar 

  24. Sobkow L, Epperlein HH, Herklotz S, Straube WL, Tanaka EM (2006) A germline GFP transgenic axolotl and its use to track cell fate: dual origin of the fin mesenchyme during development and the fate of blood cells during regeneration. Dev Biol 290:386–397

    Article  PubMed  CAS  Google Scholar 

  25. Putta S, Smith JJ, Walker JA, Rondet M, Weisrock DW, Monaghan J, Samuels AK, Kump K, King DC, Maness NJ, Habermann B, Tanaka E, Bryant SV, Gardiner DM, Parichy DM, Voss SR (2004) From biomedicine to natural history research: EST resources for ambystomatid salamanders. BMC Genomics 5:54

    Article  PubMed  Google Scholar 

  26. Smith JJ, Putta S, Walker JA, Kump DK, Samuels AK, Monaghan JR, Weisrock DW, Staben C, Voss SR (2005) Sal-site: integrating new and existing ambystomatid salamander research and informational resources. BMC Genomics 6:181

    Article  PubMed  Google Scholar 

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Acknowledgements

This study was supported by NIH grants HL061246 and HL58435 and by a Christine E. Lynn American Heart Association Grant-in-Aid to L.F.L. Some of the embryos used for this study were provided by the Axolotl Colony at University of Kentucky (NSF-DBI–0443496).

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Correspondence to L. F. Lemanski.

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Jia, P., Zhang, C., Huang, X.P. et al. A novel protein involved in heart development in Ambystoma mexicanum is localized in endoplasmic reticulum. J Biomed Sci 15, 789–799 (2008). https://doi.org/10.1007/s11373-008-9262-y

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  • DOI: https://doi.org/10.1007/s11373-008-9262-y

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