Biology subjects

Braco, J. T.

Publications and source records attributed to Braco, J. T..

2 recordsLinked to original sources

bioRxiv2025

Metabolic state modulates risky foraging behavior via multiple branches of the insulin/IGF-1-like pathway in C. elegans

Foraging to acquire nutrients is an essential and sometimes risky behavior displayed by nearly all animals. Appropriately balancing foraging risks with nutrient requirements is pivotal for peak survival and reproduction, and metabolic state (i.e., how urgently the animal requires nutrients) is a strong modulator of risky foraging behavior. In this study, we asked what molecular signal allows C. elegans to change its foraging behavior in response to changes in its metabolic state. We used an assay of risky foraging behavior, where wild type worms increase risky foraging behavior after food deprivation, to screen for candidate genes. We found that DAF-2, the singular receptor in the C. elegans insulin/IGF-1 signaling (IIS) pathway, is necessary for worms to modulate risky foraging behavior in response to short-term food deprivation. Worms with mutations in genes upstream and downstream of daf-2 in the IIS pathway also exhibited a reduction in the effect of food deprivation. While a canonical understanding of the IIS pathway would suggest that the FOXO transcription factor DAF-16 is the primary downstream IIS pathway target, we found that DAF-16 was not required for worms to exhibit food-deprivation-driven changes in foraging behavior. Furthermore, we determined that the calsyntenin ortholog CASY-1, which allows DAF-2c to traffic to axons, is required for food deprivation to modulate risky foraging behavior. These results both validate the IIS receptor as a pivotal regulator of risky foraging behavior and suggest a multi-pronged downstream pathway. Overall, these data enrich our understanding of how organisms transduce metabolic state information to make vital decisions about when to engage in risky foraging behaviors. ARTICLE SUMMARYC. elegans changes its foraging behavior from a low-risk to a high-risk strategy when it is food deprived. Our paper demonstrates that the DAF-2 insulin/IGF-1-like receptor is an essential modulator for this behavior following food deprivation. Moreover, the regulation of risky foraging behavior is enacted by multiple downstream effectors of the insulin/IGF-1-like pathway, including a canonical pathway involving the FOXO transcription factor DAF-16 and a non-canonical pathway involving CASY-1, which can traffic an isoform of DAF-2 to axons.

neuroscience↗

bioRxiv2020

Modulation of metabolic hormone signaling via a circadian hormone and a biogenic amine in Drosophila melanogaster.

In insects, Adipokinetic hormone is the primary hormone responsible for the mobilization of stored energy. While a growing body of evidence has solidified AKHs role in modulating the physiological and behavioral responses to metabolic stress, little is known about the upstream endocrine circuit that directly regulates AKH release. We evaluated the AKH-expressing cell transcriptome to identify potential regulatory elements controlling AKH cell activity, and found that a number of receptors show consistent expression levels, including all known dopamine receptors, dopamine ecdysone receptor (DopEcR), Dopamine 2-like receptor (D2R), Dopamine 1-like receptor 2 (DopR2), DopR, and the Pigment Dispersing Factor (PDFR). We tested the consequences of targeted genetic knockdown and found that RNAi elements targeting each dopamine receptor caused a significant reduction in survival under starvation. In contrast, PDFR knockdown significantly extended lifespan under starvation whereas expression of a tethered PDF in AKH cells resulted in a significantly shorter lifespan during starvation. These manipulations also caused various changes in locomotor activity under starvation. Specifically, there were higher amounts of locomotor activity in dopamine receptor knockdowns, in both replete and starved states. PDFR knockdown resulted in increased locomotion during replete conditions and locomotion levels that were comparable to wild-type during starvation. Expression of a membrane-tethered PDF led to decreased locomotion under baseline and starvation. Next, we used live-cell imaging to evaluate the acute effects of the ligands for these receptors (dopamine, ecdysone, and Pigment Dispersing Factor) on AKH cell activation. Dopamine application led to a transient increase in intracellular calcium in a sugar-dependent manner. Furthermore, we found that co-application of dopamine and ecdysone led to a complete loss of this response, suggesting that these two hormones are acting antagonistically. We also found that PDF application directly led to an increase in cAMP in AKH cells, and that this response was dependent on expression of the PDFR in AKH cells. Together these results suggest a complex circuit in which multiple hormones act on AKH cells to modulate metabolic state.

neuroscience↗