lmn-1 Regulates Dietary Restriction via the mTOR Pathway

Animals subjected to dietary restriction (DR), a conserved metabolic intervention, have a reduced body size, low fecundity, slower development and lower fat content. Mutations in human lamin A/C intermediate filaments proteins cause numerous diseases including metabolic diseases. In this study we have identified lamin as a regulators of multiple dietary restriction phenotypesis conserved in metazoan evolution. Down-regulation of lmn-1 (the C.elegans lamin gene) in DR C. elegans increases animal size and fat content. The reduced fat content in DR animals is probably due to the regulation of sbp-1 (the SREBP homologue) by lmn-1. The mechanistic target of rapamycin (mTOR) pathway is a master regulator of cell metabolism. We genetically mapped lmn-1 to the mTOR pathway, downstream of AMPK, AKT-1 and DAF-2 and upstream of S6 Kinase and RAPTOR . Furthermore, to understand the role of lamin in this metabolic pathway, we are adapting a recently described method, the BAR method, to identify lamin protein interactions with lamin in C. elegans.