title: Peroxiredoxin stabilization of DE-cadherin promotes primordial germ cell adhesion.
abstract: Regulated adhesion between cells and their environment is critical for normal cell migration. We have identified mutations in a gene encoding the Drosophila hydrogen peroxide (H₂O₂)-degrading enzyme Jafrac1, which lead to germ cell adhesion defects. During gastrulation, primordial germ cells (PGCs) associate tightly with the invaginating midgut primordium as it enters the embryo; however, in embryos from jafrac1 mutant mothers this association is disrupted, leaving some PGCs trailing on the outside of the embryo. We observed similar phenotypes in embryos from DE-cadherin/shotgun (shg) mutant mothers and were able to rescue the jafrac1 phenotype by increasing DE-cadherin levels. This and our biochemical evidence strongly suggest that Jafrac1-mediated reduction of H₂O₂ is required to maintain DE-cadherin protein levels in the early embryo. Our results present in vivo evidence of a peroxiredoxin regulating DE-cadherin-mediated adhesion.
authors.affiliation: Department of Cell Biology, HHMI and Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: DeGennaro
authors.forename: Thomas Ryan
authors.initials: TR
authors.lastname: Hurd
authors.forename: Daria Elisabeth
authors.initials: DE
authors.lastname: Siekhaus
authors.forename: Benoit
authors.initials: B
authors.lastname: Biteau
authors.forename: Heinrich
authors.initials: H
authors.lastname: Jasper
authors.forename: Ruth
authors.initials: R
authors.lastname: Lehmann
mesh_terms: D022005:Adherens Junctions / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000196:embryology / Q000201:enzymology* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D054262:Gastrulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005854:Germ Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010544:Peroxidases / Q000378:metabolism*; D055550:Protein Stability / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D015820:Cadherins; D029721:Drosophila Proteins; C501889:shg protein, Drosophila; D006861:Hydrogen Peroxide; C404709:Jafrac1 protein, Drosophila; D010544:Peroxidases