Reptin and Pontin Antagonistically Regulate Heart Growth in Zebrafish Embryos

Cell. 2002 Nov 27;111(5):661-72. doi: 10.1016/s0092-8674(02)01112-1.

Abstract

Organ size is precisely regulated during development, but the control mechanisms remain obscure. We have isolated a mutation in zebrafish, liebeskummer (lik), which causes development of hyperplastic embryonic hearts. lik encodes Reptin, a component of a DNA-stimulated ATPase complex. The mutation activates ATPase activity of Reptin complexes and causes a cell-autonomous proliferation of cardiomyocytes to begin well after progenitors have fashioned the primitive heart tube. With regard to heart growth, beta-catenin and Pontin, a DNA-stimulated ATPase that is often part of complexes with Reptin, are in the same genetic pathways. Pontin reduction phenocopies the cardiac hyperplasia of the lik mutation. Thus, the Reptin/Pontin ratio serves to regulate heart growth during development, at least in part via the beta-catenin pathway.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP-Dependent Proteases
  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / physiology
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cardiomegaly / embryology
  • Cardiomegaly / etiology
  • Cardiomegaly / genetics
  • Carrier Proteins
  • Cell Division
  • Conserved Sequence
  • Cytoskeletal Proteins / physiology
  • Embryo, Nonmammalian
  • Enzyme Activation
  • Gene Expression Regulation, Developmental
  • Heart / embryology*
  • Heat-Shock Proteins / physiology
  • Molecular Sequence Data
  • Myocardium / cytology
  • Myocardium / ultrastructure
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Point Mutation
  • Sequence Homology, Amino Acid
  • Serine Endopeptidases / physiology
  • Trans-Activators / physiology
  • Zebrafish
  • Zebrafish Proteins / chemistry
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / physiology*
  • beta Catenin

Substances

  • Carrier Proteins
  • Cytoskeletal Proteins
  • Heat-Shock Proteins
  • Nuclear Proteins
  • Trans-Activators
  • Zebrafish Proteins
  • beta Catenin
  • ctnnb1 protein, zebrafish
  • ruvbl1 protein, zebrafish
  • ruvbl2 protein, zebrafish
  • ATP-Dependent Proteases
  • Serine Endopeptidases
  • Adenosine Triphosphatases

Associated data

  • GENBANK/AY057075
  • GENBANK/AY092764