Starvation activates MAPK through the muscarinic acetylcholine pathway in Caenorhabditis elegans pharynx.

초록

In this study, we show biochemically that starvation activates MAPK (Mitogen-activated Protein Kinase), MPK-1, in the pharyngeal muscles of C elegans. Seeking the signals through which starvation acts, we found a pathway by which muscarinic acetylcholine signaling activates MAPK through a muscarinic acetylcholine receptor (GAR-3) → Gqα → nPKC (novel Protein Kinase C, TPA-1) → classical ras pathway. This pathway is activated by starvation, as shown by the following results: (1) Starvation causes phosphorylation of MPK-1 in the pharyngeal muscles (2) In a sensitized genetic background in which Gqα signaling cannot be downregulated, activation of the pathway by a muscarinic agonist causes lethal changes in pharyngeal muscle function. Starvation has identical effects. (3) Overexpression of MAPK in wild-type pharyngeal muscle mimics the effects of muscarinic agonist and of starvation on sensitized muscle. (4) A muscarinic antagonist blocks the effects of muscarinic agonist and of starvation on sensitized muscle. (5) Mutations and drugs that block any step of signaling from the muscarinic receptor to MAPK also block the effects of starvation on sensitized muscle. We suggest that during starvation the muscarinic pathway to MAPK is activated to change the pharyngeal muscle physiology so as to enhance ingestion of food when food becomes available again.