title: A novel regulatory mutation in the C. elegans sex determination gene tra-2 defines a candidate ligand/receptor interaction site.
abstract: Sex determination in the nematode C. elegans is dependent on cell-to-cell communication, which appears to be mediated by the predicted membrane protein TRA-2A and the secreted protein HER-1. In XO males, HER-1 is hypothesised to function as a repressive ligand that inactivates the TRA-2A receptor. In XX animals, HER-1 is absent and TRA-2A promotes hermaphrodite development by negatively regulating the FEM proteins. This paper describes the molecular and genetic characterisation of a novel class of feminising mutations called tra-2(eg), for enhanced gain-of-function. In XX animals, mutant tra-2(eg) activity promotes entirely normal hermaphrodite development. However, the tra-2(eg) mutations generate an XO-specific gain-of-function phenotype, because they transform XO mutants from male into hermaphrodite. Therefore, the tra-2(eg) mutations identify a major regulatory site, which may be the TRA-2A/HER-1 interaction site. All ten tra-2(eg) mutations encode identical missense changes in a predicted extracellular domain of TRA-2A, named the EG site. It is proposed that the tra-2(eg) mutation encodes a TRA-2A protein that functions constitutively in XO animals, because it is defective in HER-1 binding. Phenotypic characterisation of sexually transformed XO tra-2(eg) hermaphrodites reveals that their fertility is strongly affected by dosage compensation mutations, suggesting that dosage compensation plays a role in normal gametogenesis.
authors.affiliation: Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: P E
authors.initials: PE
authors.lastname: Kuwabara
mesh_terms: D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D018929:Cell Culture Techniques; D003001:Cloning, Molecular; D012734:Disorders of Sex Development / Q000235:genetics; D029721:Drosophila Proteins; D005262:Feminization / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000502:physiology*; D012261:Ribonucleoproteins / Q000235:genetics* / Q000378:metabolism; D012733:Sex Differentiation / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D015801:Helminth Proteins; D008024:Ligands; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D012261:Ribonucleoproteins; C079744:her-1 protein, C elegans; C066174:tra2 protein, Drosophila