LAG1 was identified as a gene whose expression decreases with increasing age of yeast cells (1). Deletion of LAG1 results in a 50% increase in the lifespan of the mutated yeast cells (1). LAC1 was identified as a close homolog of LAG1, and a double deletion of the two genes has been reported as lethal (5) or poor-growing (6). Human and C. elegans homologs of LAG1 have been cloned, and each is able to complement a lag1 lac1 double deletion (5). Lag1p and Lac1p have been localized to the endoplasmic reticulum, and are thought to play a role in the transport from the ER to the Golgi of glycosylphosphatidylinositol (GPI)-anchored proteins (6).

About sphingolipid metabolism

Sphingolipids are essential components of the plasma membrane in all eukaryotic cells. S. cerevisiae cells make three complex sphingolipids: inositol-phosphoceramide (IPC), mannose-inositol-phosphoceramide (MIPC), and mannose-(inositol phosphate)2-ceramide (M(IP)2C)(7). In the yeast plasma membrane sphingolipids concentrate with ergosterol to form lipid rafts, specialized membrane microdomains implicated in a variety of cellular processes, including sorting of membrane proteins and lipids, as well as organizing and regulating signaling cascades (8). Intermediates in sphingolipid biosynthesis have been shown to play important roles as signaling molecules and growth regulators. Sphingolipid long chain bases (LCBs), dihydrosphingosine (DHS) and phytosphingosine (PHS), have been implicated as secondary messengers in signaling pathways that regulate the heat stress response (9, 10). Other intermediates, phytoceramide and long-chain base phosphates (LCBPs), have been shown to be components of the tightly-controlled ceramide/LCBP rheostat, which regulates cell growth (11). Since phosphoinositol-containing sphingolipids are unique to fungi, the sphingolipid biosynthesis pathway is considered a target for antifungal drugs (12, 13).

Last updated: 2000-03-01