| 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
|
| Resource |
| C.elegans |
tm742 |
