title: A lipid-modified phosphoinositide-specific phospholipase C (TcPI-PLC) is involved in differentiation of trypomastigotes to amastigotes of Trypanosoma cruzi.
abstract: 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.
authors.affiliation: Department of Pathobiology and Center for Zoonoses Research, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Okura
authors.forename: Jianmin
authors.initials: J
authors.lastname: Fang
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Salto
authors.forename: Randall S
authors.initials: RS
authors.lastname: Singer
authors.forename: Roberto
authors.initials: R
authors.lastname: Docampo
authors.forename: Silvia N J
authors.initials: SN
authors.lastname: Moreno
mesh_terms: 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*
chemical_list: D008562:Membrane Glycoproteins; D016376:Oligonucleotides, Antisense; D015800:Protozoan Proteins; C088681:amastin protein, Trypanosoma cruzi; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase