title: Nucleotide levels regulate germline proliferation through modulating GLP-1/Notch signaling in C. elegans.
abstract: Animals alter their reproductive programs to accommodate changes in nutrient availability, yet the connections between known nutrient-sensing systems and reproductive programs are underexplored, and whether there is a mechanism that senses nucleotide levels to coordinate germline proliferation is unknown. We established a model system in which nucleotide metabolism is perturbed in both the nematode Caenorhabditis elegans (cytidine deaminases) and its food (Escherichia coli); when fed food with a low uridine/thymidine (U/T) level, germline proliferation is arrested. We provide evidence that this impact of U/T level on the germline is critically mediated by GLP-1/Notch and MPK-1/MAPK, known to regulate germline mitotic proliferation. This germline defect is suppressed by hyperactivation of glp-1 or disruption of genes downstream from glp-1 to promote meiosis but not by activation of the IIS or TORC1 pathways. Moreover, GLP-1 expression is post-transcriptionally modulated by U/T levels. Our results reveal a previously unknown nucleotide-sensing mechanism for controlling reproductivity.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, Colorado 80309, USA.
authors.forename: Congwu
authors.initials: C
authors.lastname: Chi
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, Colorado 80309, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Ronai
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, Colorado 80309, USA.
authors.forename: Minh T
authors.initials: MT
authors.lastname: Than
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, Colorado 80309, USA.
authors.forename: Cierra J
authors.initials: CJ
authors.lastname: Walker
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, Colorado 80309, USA.
authors.forename: Aileen K
authors.initials: AK
authors.lastname: Sewell
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, Colorado 80309, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Han
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D005298:Fertility / Q000235:genetics; D005854:Germ Cells; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D009154:Mutation; D009711:Nucleotides / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D009711:Nucleotides; D051880:Receptors, Notch; D052216:Glucagon-Like Peptide 1
keywords: CRP; HT115; cytR; gld-1; nucleotide salvage pathway; nutrient sensing
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