Activities | Families | Sequences | Fold types | References | Help
B6db references: 14609948

type Journal Article
authors Zhang, K.; Showalter, M.; Revollo, J.; Hsu, F.F.; Turk, J.; Beverley, S.M.
title Sphingolipids are essential for differentiation but not growth in Leishmania
journal EMBO J
sel selected
ui 14609948
year (2003)
volume 22
number 22
pages 6016-26.
keywords Sphingolipids/*genetics/*development
abstract Sphingolipids (SLs) play critical roles in eukaryotic cells in the formation of lipid rafts, membrane trafficking, and signal transduction. Here we created a SL null mutant in the protozoan parasite Leishmania major through targeted deletion of the key de novo biosynthetic enzyme serine palmitoyltransferase subunit 2 (SPT2). Although SLs are typically essential, spt2- Leishmania were viable, yet were completely deficient in de novo sphingolipid synthesis, and lacked inositol phosphorylceramides and other SLs. Remarkably, spt2- parasites maintained 'lipid rafts' as defined by Triton X-100 detergent resistant membrane formation. Upon entry to stationary phase spt2- failed to differentiate to infective metacyclic parasites and died instead. Death occurred not by apoptosis or changes in metacyclic gene expression, but from catastrophic problems leading to accumulation of small vesicles characteristic of the multivesicular body/multivesicular tubule network. Stage specificity may reflect changes in membrane structure as well as elevated demands in vesicular trafficking required for parasite remodeling during differentiation. We suggest that SL-deficient Leishmania provide a useful biological setting for tests of essential SL enzymes in other organisms where SL perturbation is lethal.
last changed 2004/09/14 13:43

B6db references