title: C. elegans GLA-3 is a novel component of the MAP kinase MPK-1 signaling pathway required for germ cell survival.
abstract: During oocyte development in Caenorhabditis elegans, approximately half of all developing germ cells undergo apoptosis. While this process is evolutionarily conserved from worms to humans, the regulators of germ cell death are still largely unknown. In a genetic screen for novel genes involved in germline apoptosis in Caenorhabditis elegans, we identified and cloned gla-3. Loss of gla-3 function results in increased germline apoptosis and reduced brood size due to defective pachytene exit from meiosis I. gla-3 encodes a TIS11-like zinc-finger-containing protein that is expressed in the germline, from the L4 larval stage to adulthood. Biochemical evidence and genetic epistasis analysis revealed that GLA-3 participates in the MAPK signaling cascade and directly interacts with the C. elegans MAPK MPK-1, an essential meiotic regulator. Our results show that GLA-3 is a new component of the MAPK cascade that controls meiotic progression and apoptosis in the C. elegans germline and functions as a negative regulator of the MAPK signaling pathway during vulval development and in muscle cells.
authors.affiliation: Institute of Molecular Biology, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Ekaterini A
authors.initials: EA
authors.lastname: Kritikou
authors.forename: Stuart
authors.initials: S
authors.lastname: Milstein
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Vidalain
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lettre
authors.forename: Erica
authors.initials: E
authors.lastname: Bogan
authors.forename: Kimon
authors.initials: K
authors.lastname: Doukoumetzidis
authors.forename: Phillip
authors.initials: P
authors.lastname: Gray
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Chappell
authors.forename: Marc
authors.initials: M
authors.lastname: Vidal
authors.forename: Michael O
authors.initials: MO
authors.lastname: Hengartner
mesh_terms: D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival; D005260:Female; D005854:Germ Cells / Q000166:cytology*; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008540:Meiosis; D019950:Mitogen-Activated Protein Kinase 1; D008969:Molecular Sequence Data; D032342:Muscle Cells; D016296:Mutagenesis; D009154:Mutation; D025941:Protein Interaction Mapping; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D019076:Transgenes; D051816:Tristetraprolin / Q000235:genetics / Q000378:metabolism*; D014844:Vulva / Q000196:embryology
chemical_list: D029742:Caenorhabditis elegans Proteins; C513401:GLA-3 protein, C elegans; D051816:Tristetraprolin; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; C085697:mpk-1 protein, C elegans