Previous Article | Next Article ![]()
Molecular and Cellular Biology, September 2001, p. 6198-6209, Vol. 21, No. 18
Infectious Diseases Research, Lilly Research
Laboratories, Eli Lilly and Company, Lilly Corporate Center,
Indianapolis, Indiana 46285
Received 1 May 2001/Returned for modification 4 June 2001/Accepted 25 June 2001
Sphingolipids are major components of the plasma membrane of
eukaryotic cells and were once thought of merely as structural components of the membrane. We have investigated effects of inhibiting sphingolipid biosynthesis, both in germinating spores and growing hyphae of Aspergillus nidulans. In germinating spores,
genetic or pharmacological inactivation of inositol phosphorylceramide (IPC) synthase arrests the cell cycle in G1 and also
prevents polarized growth during spore germination. However,
inactivation of IPC synthase not only eliminates sphingolipid
biosynthesis but also leads to a marked accumulation of ceramide, its
upstream intermediate. We therefore inactivated serine
palmitoyltransferase, the first enzyme in the sphingolipid biosynthesis
pathway, to determine effects of inhibiting sphingolipid biosynthesis
without an accumulation of ceramide. This inactivation also prevented polarized growth but did not affect nuclear division of germinating spores. To see if sphingolipid biosynthesis is required to maintain polarized growth, and not just to establish polarity, we inhibited sphingolipid biosynthesis in cells in which polarity was already established. This inhibition rapidly abolished normal cell polarity and
promoted cell tip branching, which normally never occurs. Cell tip
branching was closely associated with dramatic 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 control of the actin
cytoskeleton and that accumulation of ceramide is likely responsible
for arresting the cell cycle in G1.
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.18.6198-6209.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Cell Cycle Progression and Cell Polarity Require
Sphingolipid Biosynthesis in Aspergillus
nidulans
*
Corresponding author. Mailing address: Infectious
Diseases Research, Lilly Research Laboratories, Eli Lilly and Company,
Lilly Corporate Center, Indianapolis, IN 46285. Phone: (317) 277-1467. Fax: (317) 277-0778. E-mail: Ye_Xiang{at}lilly.com.
This article has been cited by other articles:
| J. Bacteriol. | J. Virol. | Eukaryot. Cell |
|---|
| Microbiol. Mol. Biol. Rev. | Clin. Vaccine Immunol. | All ASM Journals |
|---|