A functional study of all 40 Caenorhabditis elegans insulin-like peptides

Abstract

The human genome encodes 10 insulin-like genes, whereas the <i>Caenorhabditis elegans</i> genome remarkably encodes 40 insulin-like genes. Knockout strategies to determine the roles of all the insulin/insulin-like peptide ligands (INS) in <i>C. elegans</i> has been challenging due to functional redundancy. Here, we individually overexpressed each of the 40 <i>ins</i> genes pan-neuronally, and monitored multiple phenotypes including: L1 arrest life span, neuroblast divisions under L1 arrest, dauer formation, and fat accumulation, as readouts to characterize the functions of each INS <i>in vivo</i> Of the 40 INS peptides, we found functions for 35 INS peptides and functionally categorized each as agonists, antagonists, or of pleiotropic function. In particular, we found that 9 of 16 agonistic INS peptides shortened L1 arrest life span and promoted neuroblast divisions during L1 arrest. Our study revealed that a subset of β-class INS peptides that contain a distinct F peptide sequence are agonists. Our work is the first to categorize the structures of INS peptides and relate these structures to the functions of all 40 INS peptides <i>in vivo</i> Our findings will promote the study of insulin function on development, metabolism, and aging-related diseases.