Intestinal Mg(2+) accumulation induced by cnnm mutations decreases the body size by suppressing TORC2 signaling in Caenorhabditis elegans.

Mg2+ is a vital ion involved in diverse cellular functions by forming complexes with ATP. Intracellular Mg2+ levels are tightly regulated by the coordinated actions of multiple Mg2+ transporters, such as the Mg2+ efflux transporter, cyclin M (CNNM). Caenorhabditis elegans (C. elegans) worms with mutations in both cnnm-1 and cnnm-3 exhibit excessive Mg2+ accumulation in intestinal cells, leading to various phenotypic abnormalities. In this study, we investigated the mechanism underlying the reduction in body size in cnnm-1; cnnm-3 mutant worms. RNA interference (RNAi) of gtl-1, which encodes a Mg2+-intake channel in intestinal cells, restored the worm body size, confirming that this phenotype is due to excessive Mg2+ accumulation. Moreover, RNAi experiments targeting body size-related genes and analyses of mutant worms revealed that the suppression of the target of rapamycin complex 2 (TORC2) signaling pathway was involved in body size reduction, resulting in downregulated DAF-7 expression in head ASI neurons. As the DAF-7 signaling pathway suppresses dauer formation under stress, cnnm-1; cnnm-3 mutant worms exhibited a greater tendency to form dauer upon induction. Collectively, our results revealed that excessive accumulation of Mg2+ repressed the TORC2 signaling pathway in C. elegans worms and suggest the novel role of the DAF-7 signaling pathway in the regulation of their body size.

Hashizume O ，Kawabe T ，Funato Y ，Miki H ... -  《-》

Mg2+ Extrusion from Intestinal Epithelia by CNNM Proteins Is Essential for Gonadogenesis via AMPK-TORC1 Signaling in Caenorhabditis elegans.

Ishii T ，Funato Y ，Hashizume O ，Yamazaki D ，Hirata Y ，Nishiwaki K ，Kono N ，Arai H ，Miki H ... -  《PLoS Genetics》

A non-canonical role for the C. elegans dosage compensation complex in growth and metabolic regulation downstream of TOR complex 2.

Webster CM ，Wu L ，Douglas D ，Soukas AA ... -  《-》

Rictor/TORC2 mediates gut-to-brain signaling in the regulation of phenotypic plasticity in C. elegans.

O'Donnell MP ，Chao PH ，Kammenga JE ，Sengupta P ... -  《PLoS Genetics》

Rictor/TORC2 regulates Caenorhabditis elegans fat storage, body size, and development through sgk-1.

Jones KT ，Greer ER ，Pearce D ，Ashrafi K ... -  《-》