Language
English
Publication Date
5-1-2025
Journal
PLOS Genetics
DOI
10.1371/journal.pgen.1011425
PMID
40446206
PMCID
PMC12151481
PubMedCentral® Posted Date
5-30-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Metabolism is fundamental to organism physiology and pathology. From the intricate network of metabolic reactions, diverse chemical molecules, collectively termed metabolites, are produced. In multicellular organisms, metabolite communication between different tissues is vital for maintaining homeostasis and adaptation. However, the molecular mechanisms mediating these metabolite communications remain poorly understood. Here, we focus on nucleosides and nucleotides, essential metabolites involved in multiple cellular processes, and report the pivotal role of the SLC29A family of transporters in mediating nucleoside coordination between the soma and the germline. Through genetic analysis, we discovered that two Caenorhabditis elegans homologs of SLC29A transporters, Equilibrative Nucleoside Transporter ENT-1 and ENT-2, act in the germline and the intestine, respectively, to regulate reproduction. Their knockdown synergistically results in sterility. Further single-cell transcriptomic and targeted metabolomic profiling revealed that the ENT double knockdown specifically affects genes in the purine biosynthesis pathway and reduces the ratio of guanosine to adenosine levels. Importantly, guanosine supplementation into the body cavity/pseudocoelom through microinjection rescued the sterility caused by the ENT double knockdown, whereas adenosine microinjection had no effect. Together, these studies support guanosine as a rate-limiting factor in the control of reproduction, uncover the previously unknown nucleoside/nucleotide communication between the soma and the germline essential for reproductive success, and highlight the significance of SLC-mediated cell-nonautonomous metabolite coordination in regulating organism physiology.
Keywords
Animals, Caenorhabditis elegans, Reproduction, Caenorhabditis elegans Proteins, Guanosine, Germ Cells, Equilibrative Nucleoside Transporter 1, Equilibrative-Nucleoside Transporter 2, Nucleosides, Adenosine, Nucleoside Transport Proteins
Published Open-Access
yes
Recommended Citation
Guan, Youchen; Yu, Yong; Gao, Shihong M; et al., "Cross-Tissue Coordination Between Slc Nucleoside Transporters Regulates Reproduction in Caenorhabditis elegans" (2025). Faculty, Staff and Students Publications. 6473.
https://digitalcommons.library.tmc.edu/baylor_docs/6473