An Insulin-to-Insulin Regulatory Network Orchestrates Phenotypic Specificity in Development and Physiology

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Insulin signaling is widely implicated in regulating diverse physiological processes ranging from metabolism to longevity across many animal species. Many animals have multiple insulin-like peptides that can regulate the activity of this signaling pathway. For example, while humans have ten, including the well-studied insulin hormone, the nematode Caenorhabditis elegans has forty such peptides. The similarity among these insulin-like peptides led to the predominant notion that widespread redundancy occurs among these peptides. Contrary to this notion, we find that the forty insulin-like peptides in the nematode C. elegans have specific and distinct effects on eight different physiological outputs that range from development, stress responses, lifespan and reproduction. Interestingly, we also find that these peptides regulate each other at the transcriptional level to form a signaling network. In addition, we observe that this network is organized into parallel circuits, whose activities are affected by compensation, feedback and crosstalk. Finally, the organization of the network helps to explain how different combinations of peptides generate specific outputs and captures the complexity of how these peptides orchestrate an animal's physiology through distinct peptide-to-peptide signaling circuits.

Vyšlo v časopise: An Insulin-to-Insulin Regulatory Network Orchestrates Phenotypic Specificity in Development and Physiology. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004225
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004225

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