Calcineurin B of the human protozoan parasite Trypanosoma cruzi is involved in cell invasion

Jorge E. Araya, Alberto Cornejo, Patricio R. Orrego, Esteban M. Cordero, Mauro Cortéz, Héctor Olivares, Ivan Neira, Hernán Sagua, José Franco da Silveira, Nobuko Yoshida, Jorge González

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

During Trypanosoma cruzi cell invasion, signal transduction pathways are triggered in parasite and host cells, leading to a rise in intracellular Ca2+ concentration. We posed the question whether calcineurin (CaN), in particular the functional regulatory subunit CaNB, a Ca2+-binding EF-hand protein, was expressed in T. cruzi and whether it played a role in cell invasion. Here we report the cloning and characterization of CL strain CaNB gene, as well as the participation of CaNB in cell invasion. Treatment of metacyclic trypomastigotes (MT) or tissue-culture trypomastigotes (TCT) with the CaN inhibitors cyclosporin or cypermethrin strongly inhibited (62-64%) their entry into HeLa cells. In assays using anti-phospho-serine/threonine antibodies, a few proteins of MT were found to be dephosphorylated in a manner inhibitable by cyclosporin upon exposure to HeLa cell extract. The phosphatase activity of CaN was detected by a biochemical approach in both MT and TCT. Treatment of parasites with antisense phosphorothioate oligonucleotides directed to TcCaNB-CL, which reduced the expression of TcCaNB and affected TcCaN activity, resulted in ∼50% inhibition of HeLa cell entry by MT or TCT. Given that TcCaNB-CL may play a key role in cell invasion and differs considerably in its primary structure from the human CaNB, it might be considered as a potential chemotherapeutic target.

Original languageEnglish
Pages (from-to)892-900
Number of pages9
JournalMicrobes and Infection
Volume10
Issue number8
DOIs
Publication statusPublished - Jul 2008

Keywords

  • Antisense oligonucleotides
  • Ca mobilization
  • Calcineurin B
  • Cell invasion
  • Inhibitors
  • Phosphatase activity
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Calcineurin B of the human protozoan parasite Trypanosoma cruzi is involved in cell invasion'. Together they form a unique fingerprint.

Cite this