Regulation of Caenorhabditis elegans vitellogenesis by DAF-2/IIS through separable transcriptional and posttranscriptional mechanisms

Abstract

BackgroundEvolutionary theories of aging propose that longevity evolves as a competition between reproduction and somatic maintenance for a finite pool of resources. Reproduction is thought to shorten lifespan by depleting resources from processes promoting somatic maintenance. Maternal yolk production, vitellogenesis, represents a significant maternal cost for reproduction and is suppressed under genetic and environmental conditions that extend lifespan. However, little is known about the pathways regulating vitellogenesis in response to prolongevity cues.ResultsIn order to identify mechanisms that suppress vitellogenesis under prolongevity conditions, we studied factors regulating vitellogenesis in C. elegans nematodes. In C. elegans, vitellogenesis is depressed in the absence of insulin-like signaling (IIS). We found that the C. elegans daf-2/IIS pathway regulates vitellogenesis through two mechanisms. vit-2 transcript levels in daf-2 mutants were indirectly regulated through a germline-dependent signal, and could be rescued by introduction of daf-2(+) sperm. However, yolk protein (YP) levels in daf-2 mutants were also regulated by germline-independent posttranscriptional mechanisms.ConclusionsC. elegans vitellogenesis is regulated transcriptionally and posttranscriptionally in response to environmental and reproductive cues. The daf-2 pathway suppressed vitellogenesis through transcriptional mechanisms reflecting reproductive phenotypes, as well as distinct posttranscriptional mechanisms. This study reveals that pleiotropic effects of IIS pathway mutations can converge on a common downstream target, vitellogenesis, as a mechanism to modulate longevity.

Alternative Perspectives on Aging inCaenorhabditis elegans: Reactive Oxygen Species or Hyperfunction?

“…For example, knockdown of expression of vit-2 and vit-5 increased lifespan (40), and yolk levels are greatly reduced in long-lived daf-2 insulin/ IGF-1 receptor mutants (12). Similarities have been noted between worm yolk (lipoprotein) particles and mammalian apoB-dependent low-density lipoprotein (LDL) (9,45).…”

“…In worms with sperm, VIT-2::GFP is seen only in the intestine and oocytes. When sperm depletes, yolk rapidly appears throughout the worm, particularly in the body cavity, where it accumulates to high levels (12,15,24,37) (Fig. 3).…”

“…In each part, young adult worm is shown above and an older worm below. Redrawn after published observations (12,15,18,24,27,37,48).…”

Sex Differences: A Resultant of an Evolutionary Pressure?

“…Vitellogenins are multi-domain apolipoproteins synthesized in adult females in a very restricted number of cells. In the adult hermaphrodite of C. elegans, vitellogenesis occurs in the intestine only and the proteins generated are co-translationally secreted in the body cavity to reach the gonads where are taken up by a LDL-like receptor (DePina et al, 2011). In these organisms, vitellogenin synthesis is under the strict, dual control of gonadal secretion (sperm production) and nutrient levels (through the insulin/IGF-1 signaling (IIS)/daf-2 pathway).…”

A microRNA program in the C. elegans hypodermis couples to intestinal mTORC2/PQM-1 signaling to modulate fat transport

“…One such regulatory input is insulin/insulin-like growth factor (IGF) signaling, which mediates key aspects of C. elegans growth, development, metabolism, and reproduction but is also required for vitellogenesis (Murphy et al 2003;DePina et al 2011). Although insulin-like signaling is required for vitellogenesis, it is unlikely to be the sole regulatory input, and additional pathways or genetic modifiers are likely to exist.…”