A lipid-modified phosphoinositide-specific phospholipase C (TcPI-PLC) is involved in differentiation of trypomastigotes to amastigotes of Trypanosoma cruzi

被引:36
作者
Okura, M
Fang, JM
Salto, ML
Singer, RS
Docampo, R
Moreno, SNJ [1 ]
机构
[1] Univ Georgia, Ctr Trop & Global Emerging Dis, Athens, GA 30602 USA
[2] Univ Illinois, Dept Pathobiol, Urbana, IL 61802 USA
[3] Univ Illinois, Ctr Zoonoses Res, Urbana, IL 61802 USA
[4] Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA
关键词
D O I
10.1074/jbc.M414535200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The phosphoinositide-specific phospholipase C ( PIPLC) is an important component of the inositol phosphate/ diacylglycerol signaling pathway. A newly discovered Trypanosoma cruzi PI-PLC (TcPI-PLC) is lipid modified in its N terminus, targeted to its plasma membrane, and believed to play a role in differentiation of the parasite because its expression increases during the differentiation of trypomastigote to amastigote stages. To determine whether TcPI-PLC is involved in this differentiation step, antisense inhibition using phosphorothioate-modified oligonucleotides, and overexpression of the gene were performed. Antisense oligonucleotide-treated parasites showed a reduced rate of differentiation in comparison to controls, as well as accumulation of intermediate forms. Overexpression of TcPI-PLC led to a faster differentiation rate. In contrast, overexpression of a mutant TcPI-PLC that lacked the lipid modification at its N terminus did not affect the differentiation rate. Therefore, TcPI-PLC is involved, when expressed in the plasma membrane, in the differentiation of trypomastigotes to amastigotes, an essential step for the intracellular replication of these parasites.
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收藏
页码:16235 / 16243
页数:9
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