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Please use this identifier to cite or link to this item: http://hdl.handle.net/10023/1641
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Title: The essential neutral sphingomyelinase is involved in the trafficking of the variant surface glycoprotein in the bloodstream form of Trypanosoma brucei
Authors: Young, Simon A.
Smith, Terry K.
Keywords: Gpi-anchored proteins
Inositol phosphorylceramide synthase
Sleeping sickness parasite
De-novo synthesis
Saccharomyces-cerevisiae
Sphingolipid synthesisv
African trypanosomes
Phospholipase-c
Plasmodium-falciparum
Escherichia-coli
QH301 Biology
Issue Date: Jun-2010
Citation: Young , S A & Smith , T K 2010 , ' The essential neutral sphingomyelinase is involved in the trafficking of the variant surface glycoprotein in the bloodstream form of Trypanosoma brucei ' Molecular Microbiology , vol 76 , no. 6 , pp. 1461-1482 .
Abstract: Sphingomyelin is the main sphingolipid in Trypanosoma brucei, the causative agent of African sleeping sickness. In vitro and in vivo characterization of the T. brucei neutral sphingomyelinase demonstrates that it is directly involved in sphingomyelin catabolism. Gene knockout studies in the bloodstream form of the parasite indicate that the neutral sphingomyelinase is essential for growth and survival, thus highlighting that the de novo biosynthesis of ceramide is unable to compensate for the loss of sphingomyelin catabolism. The phenotype of the conditional knockout has given new insights into the highly active endocytic and exocytic pathways in the bloodstream form of T. brucei. Hence, the formation of ceramide in the endoplasmic reticulum affects post-Golgi sorting and rate of deposition of newly synthesized GPI-anchored variant surface glycoprotein on the cell surface. This directly influences the corresponding rate of endocytosis, via the recycling endosomes, of pre-existing cell surface variant surface glycoprotein. The trypanosomes use this coupled endocytic and exocytic mechanism to maintain the cell density of its crucial variant surface glycoprotein protective coat. TbnSMase is therefore genetically validated as a drug target against African trypanosomes, and suggests that interfering with the endocytic transport of variant surface glycoprotein is a highly desirable strategy for drug development against African trypanosomasis.
Version: Publisher PDF
Status: Peer reviewed
URI: http://hdl.handle.net/10023/1641
DOI: http://dx.doi.org/10.1111/j.1365-2958.2010.07151.x
ISSN: 0950-382X
Type: Journal article
Rights: (c)2010 Blackwell Publishing Ltd. Article available under Online Open option.
Appears in Collections:University of St Andrews Research
Biology Research
Biomedical Sciences Research Complex (BSRC) Research



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