THE NEUROPEPTIDE NEUROMEDIN U RECEPTOR NMUR-1 BUFFERS INSULIN RECEPTOR SIGNALING IN BACTERIA-DEPENDENT SURVIVAL.

Distinct microbial environments exert diverse effects on the physiology and survival of the nematode . Here, we show that grown on two strains exhibit different survival dynamics. Wild-type on the B type OP50 exhibit more early deaths compared to on K-12 type CS180. These early deaths on OP50 are characterized by swollen pharynges (P-deaths) due to bacterial accumulation within the tissue. In contrast, animals on CS180 are more resistant to P-deaths. These bacteria-dependent differences in P-deaths depend on bacterial lipopolysaccharide structures and the activities of the neuropeptide neuromedin U receptor , which reduces P-deaths on OP50, but not on CS180. Surprisingly, however, promotes the opposite response when the insulin receptor DAF-2 has decreased activity - where now stimulates P-deaths on OP50, but again with no effect on CS180. We also find that acts in sensory neurons to promote its bi-directional effects on longevity, which depend on the FOXO transcription factor . regulates the expression of the insulin-like peptide , which further suggests a regulatory mechanism that maintains insulin receptor DAF-2 signaling at a suitable level. Thus, our studies reveal that serves to buffer the dynamic range of DAF-2 signaling, thereby optimizing pharyngeal health and survival in response to specific bacteria.