A lipid-modified phosphoinositide-specific phospholipase C (TcPI-PLC) is involved in differentiation of trypomastigotes to amastigotes of Trypanosoma cruzi.
The phosphoinositide-specific phospholipase C (PI-PLC) 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.
Okura
Michael
M
Department of Pathobiology and Center for Zoonoses Research, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, USA.
Fang
Jianmin
J
Salto
Maria Laura
ML
Singer
Randall S
RS
Docampo
Roberto
R
Moreno
Silvia N J
SN
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D016014:Linear Models; D008562:Membrane Glycoproteins / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D043265:Phosphatidylinositol Diacylglycerol-Lyase / Q000235:genetics / Q000378:metabolism*; D054801:Phosphoinositide Phospholipase C; D015800:Protozoan Proteins / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000166:cytology / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development*
D008562:Membrane Glycoproteins; D016376:Oligonucleotides, Antisense; D015800:Protozoan Proteins; C088681:amastin protein, Trypanosoma cruzi; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase