Studies in budding yeast, Saccharomyces cerevisiae, have established an important role for the target of rapamycin (TOR) signaling network in regulating cell growth and cell architecture through the control of gene expression, protein biosynthesis, protein trafficking, as well as organization of the actin cytoskeleton. The central component of this network is the TOR kinase, which assembles into two distinct membrane associated protein complexes, termed TORC1 and TORC2, where TORC1 is uniquely inhibited by rapamycin. A novel role for this network, in particular involving TORC2, has emerged recently with respect to the regulation of the biosynthesis of sphingolipids. Complex sphingolipids are integral components of cell membranes and their biosynthesis involves the production of important bioactive intermediates, including sphingoid long-chain bases (LCBs) and ceramides, which play distinct signaling roles crucial for cell growth and survival. Here, we review recent results demonstrating a role for TORC2 in the balanced production of these intermediates and discuss how this regulation appears to involve two distinct downstream effector branches of TORC2, namely, the plextrin homology (PH) domain containing proteins SLM1 and SLM2, as well as the AGC kinases YPK1 and YPK2. We describe how these components interact with other effectors of sphingolipid metabolism and impinge on actin cytoskeletal organization, stress response, and cell survival. Finally, we discuss the likely relevance of these findings for mammalian cells.
ASJC Scopus subject areas
- Molecular Biology