RRC ID 53458
Author Chi C, Ronai D, Than MT, Walker CJ, Sewell AK, Han M.
Title Nucleotide levels regulate germline proliferation through modulating GLP-1/Notch signaling in C. elegans.
Journal Genes Dev
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.
Volume 30(3)
Pages 307-20
Published 2016-2-1
DOI 10.1101/gad.275107.115
PII 30/3/307
PMID 26833730
PMC PMC4743060
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cell Proliferation / genetics Escherichia coli / genetics Fertility / genetics Germ Cells Glucagon-Like Peptide 1 / metabolism* Mutation Nucleotides / metabolism* Receptors, Notch / metabolism* Signal Transduction*
IF 9.527
Times Cited 21
C.elegans tm742