Cell cycle progression and cell polarity require sphingolipid biosynthesisin Aspergillus nidulans

Sphingolipids are major components of the plasma membrane of eukaryotic cel ls and were once thought of merely as structural components of the membrane . We have investigated effects of inhibiting sphingolipid biosynthesis, bot h in germinating spores and growing hyphae of Aspergillus nidulans. In germ inating spores, genetic or pharmacological inactivation of inositol phospho rylceramide (IPC) synthase arrests the cell cycle in G(1) and also prevents polarized growth during spore germination. However, inactivation of PC syn thase not only eliminates sphingolipid biosynthesis but also leads to a mar ked accumulation of ceramide, its upstream intermediate. We therefore inact ivated serine palmitoyltransferase, the first enzyme in the sphingolipid bi osynthesis, pathway, to determine effects of inhibiting sphingolipid biosyn thesis without an accumulation of ceramide. This inactivation also prevente d polarized growth but did not affect nuclear division of germinating spore s. To see if sphingolipid biosynthesis is required to maintain polarized gr owth, and not just to establish polarity, we inhibited sphingolipid biosynt hesis in cells in which polarity was already established. This inhibition r apidly abolished normal cell polarity and promoted cell tip branching, whic h normally never occurs. Cell tip branching was closely associated with dra matic changes in the normally highly polarized actin cytoskeleton and found to be dependent on actin function. The results indicate that sphingolipids are essential for the establishment and maintenance of cell polarity via c ontrol of the actin cytoskeleton and that accumulation of ceramide is likel y responsible for arresting the cell cycle in G(1).