Abstract
BackgroundThe C. elegans gene folt-1 is an ortholog of the human reduced folate carrier gene. The FOLT-1 protein has been shown to transport folate and to be involved in uptake of exogenous folate by worms. A knockout mutation of the gene, folt-1(ok1460), was shown to cause sterility, and here we investigate the source of the sterility and the effect of the folt-1 knockout on somatic function.ResultsOur results show that folt-1(ok1460) knockout hermaphrodites have a substantially reduced germline, generate a small number of functional sperm, and only rarely produce a functional oocyte. We found no evidence of increased apoptosis in the germline of folt-1 knockout mutants, suggesting that germline proliferation is defective. While folt-1 knockout males are fertile, their rate of spermatogenesis was severely diminished, and the males were very poor maters. The mating defect is likely due to compromised metabolism and/or other somatic functions, as folt-1 knockout hermaphrodites displayed a shortened lifespan and elongated defecation intervals.ConclusionsThe FOLT-1 protein function affects both the soma and the germline. folt-1(ok1460) hermaphrodites suffer severely diminished lifespan and germline defects that result in sterility. Germline defects associated with folate deficiency appear widespread in animals, being found in humans, mice, fruit flies, and here, nematodes.
Highlights
The C. elegans gene folt-1 is an ortholog of the human reduced folate carrier gene
A more comprehensive study of six genes involved in folate metabolism found that the risk associated with the A80G polymorphism appears to stem from an interaction with a polymorphism in cystathionine β-synthase [22], a gene involved in the production of cystathionine from homocysteine [23], suggesting a complex set of interactions between reduced folate carrier (RFC) and other folate metabolism genes
Our results showed the cause of sterility to be due to defects in germline proliferation, and that the folt-1 knockout leads to diminished C. elegans life span and metabolism
Summary
The C. elegans gene folt-1 is an ortholog of the human reduced folate carrier gene. The FOLT-1 protein has been shown to transport folate and to be involved in uptake of exogenous folate by worms. Three different systems are responsible for folate uptake: the folate receptors [7], the reduced folate carrier (RFC) [8], and the proton coupled folate transporter (PCFT) [9]. The reduced folate carrier is a major folate transport system in mammalian cells and plays an important role in cell growth and development [10]. Supplementation with dietary folate during pregnancy is effective in preventing the incidence of neural tube defects by approximately 70% [16,17]. Genetic variation in the human RFC gene (hRFC) may influence the incidence of folate deficiency defects. Studies have shown that individuals homozygous for a polymorphism (A80G) in hRFC have a slightly higher risk of neural tube defects [18,19] and benefit more from folate supplementation [20,21]. It appears that severe folate deficiency produces embryonic failure in a diversity of species
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
