The GTPase TcRjl of the human pathogen Trypanosoma cruzi is involved in the cell growth and differentiation

• Published in: Biochemical and biophysical research communications 2012-03, Vol.419 (1), p.38-42
• Main Authors: dos Santos, Guilherme Rodrigo Reis Monteiro, Nepomuceno-Silva, José Luciano, de Melo, Luiz Dione Barbosa, Meyer-Fernandes, José Roberto, Salmon, Didier, Azevedo-Pereira, Ricardo Luiz, Lopes, Ulisses Gazos
• Format: Article
• Language: English
• Subjects: Cell Differentiation; Cell Proliferation; Guanosine Triphosphate - chemistry; Guanosine Triphosphate - metabolism; Host-Parasite Interactions; Humans; Metacyclogenesis; Monomeric GTP-Binding Proteins - chemistry; Monomeric GTP-Binding Proteins - genetics; Monomeric GTP-Binding Proteins - metabolism; Ras-like GTPase; RJL GTPase; Trypanosoma cruzi; Trypanosoma cruzi - cytology; Trypanosoma cruzi - enzymology; Trypanosoma cruzi - growth & development
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2012.01.119

► TcRjl is a Ras-related GTPase described in Trypanosoma cruzi. ► TcRjl is mainly found in the GTP-bound state in T. cruzi. ► TcRjl is localized closed to the flagellar apparatus. ► TcRjl function is required for cell growth. ► TcRjl overexpression blocks T. cruzi metacyclogenesis. The protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas Disease, undergoes through a complex life cycle where rounds of cell division and differentiation occur initially in the gut of triatominae vectors and, after transmission, inside of infected cells in vertebrate hosts. Members of the Ras superfamily of GTPases are molecular switches which play pivotal regulatory functions in cell growth and differentiation. We have previously described a novel GTPase in T. cruzi, TcRjl, which belongs to the RJL family of Ras-related GTP binding proteins. Here we show that most of TcRjl protein is found bound to GTP nucleotides and may be locked in this stage. In addition, we show that TcRjl is located close to the kinetoplast, in a region corresponding possibly to flagellar pocket of the parasite and the expression of a dominant-negative TcRjl construct (TcRjlS37N) displays a significative growth phenotype in reduced serum medium. Remarkably, overexpression of TcRjl inhibits differentiation of epimastigotes to trypomastigote forms and promotes the accumulation of intermediate differentiation stages. Our data suggest that TcRjl might play a role in the control of the parasite growth and differentiation.