Dietary vitamin B5 positively regulates intestinal neuropeptide secretion in C. elegans

Abstract

Vitamin B5 is an essential vitamin that must be acquired via diet or by the gut microbiota, and vitamin B5 deficiency or altered vitamin B5 metabolism leads to a variety of physiological and neuronal disorders. We conducted a genetic analysis of the effects of exogenous vitamin B5 in C. elegans, and we found that vitamin B5 confers protection to toxicity caused by oxidative stress and acute exposure to vitamin B5 positively regulates neuropeptide secretion. We identified a sodium-dependent multivitamin transporter family member, smvt-1 that is required for B5 uptake into cells and for protection conferred by vitamin B5. Vitamin B5 positively regulates the intestinal secretion of FLP-2, a neuropeptide-like protein whose release activates the antioxidant response. Vitamin B5 promotes FLP-2 secretion rapidly, specifically, and in a manner that is dependent upon uptake into intestinal cells by smvt-1. Vitamin B5-induced neuropeptide secretion is strictly dependent upon the SNARE protein aex-4/SNAP-25 and on the calcium dependent protein kinase C family member, pkc-2/PKCa in the intestine. These results reveal a previously uncharacterized function for dietary vitamin B5 in positively regulating intestinal neuropeptide secretion from dense core vesicles and in shaping the antioxidant response.