Original Research ARTICLE
Rac1/WAVE2 and Cdc42/N-WASP participation in actin-dependent host cell invasion by Extracellular Amastigotes of Trypanosoma cruzi
- 1Microbiologia, Imunologia e Parasitologia, Federal University of São Paulo, Brazil
This study evaluated the participation of host cell Rho-family GTPases and their effector proteins in the actin-dependent invasion by Trypanosoma cruzi extracellular amastigotes. We observed that all proteins were recruited and colocalized with actin at EA invasion sites in live or fixed cells. EA internalization was inhibited in cells depleted in Rac1, N-WASP and WAVE2. Time-lapse experiments with Rac1, N-WASP and WAVE2 depleted cells revealed that EA internalization kinetics is delayed even though no differences were observed in the proportion of EA-induced actin recruitment in these groups. Overexpression of constitutively active constructs of Rac1 and RhoA altered the morphology of actin recruitments to EA invasion sites. Additionally, EA internalization was increased in cells overexpressing CA-Rac1 but inhibited in cells overexpressing CA-RhoA. WT-Cdc42 expression increased EA internalization, but curiously, CA-Cdc42 inhibited it. Altogether, these results corroborate the hypothesis of EA internalization in non-phagocytic cells by a phagocytosis-like mechanism and present Rac1 as the key Rho-family GTPase in this process.
Keywords: Trypanosoma cruzi, extracellular amastigotes, Rho GTPases, Actin, host cell invasion
Received: 28 Nov 2017;
Accepted: 15 Feb 2018.
Edited by:Celio G. Freire-de-Lima, Universidade Federal do Rio de Janeiro, Brazil
Reviewed by:Emile S. Barrias, Instuto Nacional de Metrologia, Qualidade e Tecnologia, Brazil
Rodrigo A. López-Muñoz, Universidad Austral de Chile, Chile
Copyright: © 2018 Bonfim-Melo, Ferreira and Mortara. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Renato A. Mortara, Federal University of São Paulo, Microbiologia, Imunologia e Parasitologia, São Paulo, Brazil, firstname.lastname@example.org