Abstract
For most organisms, food is only intermittently available; therefore, molecular mechanisms that couple sensation of nutrient availability to growth and development are critical for survival. These mechanisms, however, remain poorly defined. In the absence of nutrients, newly hatched first larval (L1) stage Caenorhabditis elegans halt development and survive in this state for several weeks. We isolated mutations in unc-31, encoding a calcium-activated regulator of neural dense-core vesicle release, which conferred enhanced starvation survival. This extended survival was reminiscent of that seen in daf-2 insulin-signaling deficient mutants and was ultimately dependent on daf-16, which encodes a FOXO transcription factor whose activity is inhibited by insulin signaling. While insulin signaling modulates metabolism, adult lifespan, and dauer formation, insulin-independent mechanisms that also regulate these processes did not promote starvation survival, indicating that regulation of starvation survival is a distinct program. Cell-specific rescue experiments identified a small subset of primary sensory neurons where unc-31 reconstitution modulated starvation survival, suggesting that these neurons mediate perception of food availability. We found that OCR-2, a transient receptor potential vanilloid (TRPV) channel that localizes to the cilia of this subset of neurons, regulates peptide-hormone secretion and L1 starvation survival. Moreover, inactivation of ocr-2 caused a significant extension in adult lifespan. These findings indicate that TRPV channels, which mediate sensation of diverse noxious, thermal, osmotic, and mechanical stimuli, couple nutrient availability to larval starvation survival and adult lifespan through modulation of neural dense-core vesicle secretion.
Highlights
IntroductionMost animals are faced with fluctuating food availability
In their natural environments, most animals are faced with fluctuating food availability
We found that inactivation of ocr-2, encoding a transient receptor potential vanilloid (TRPV) channel that localizes to these sensory cilia, extended larval starvation survival as well as conferring extended adult lifespan in a DAF-16/ FOXO dependent manner
Summary
Most animals are faced with fluctuating food availability. The ability to appropriately gauge food availability to initiate programs of growth or arrest is of considerable survival value during starvation. The ability to withstand nutrient deprivation is critical for C. elegans survival, as this organism is often found in a starved state in its natural environments [3]. In the absence of food, newly hatched L1 animals arrest development and remain in this diapause state until nutrient is available. L1s in diapause are morphologically similar to well-fed siblings at the same stage This is in contrast to animals in the hibernating dauer stage, an alternative developmental state characterized by extensive morphological rearrangements (reviewed in [4]). Analysis of L1 diapause provides an opportunity to elucidate starvation survival mechanisms independent of concomitant developmental programs
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