Small GTPase Rab21 mediates fibronectin induced actin reorganization in Entamoeba histolytica: implications in pathogen invasion

PLoS Pathog. 2015 Mar 2;11(3):e1004666. doi: 10.1371/journal.ppat.1004666. eCollection 2015 Mar.

Abstract

The protozoan parasite Entamoeba histolytica causes a wide spectrum of intestinal infections. In severe cases, the trophozoites can breach the mucosal barrier, invade the intestinal epithelium and travel via the portal circulation to the liver, where they cause hepatic abscesses, which can prove fatal if left untreated. The host Extra Cellular Matrix (ECM) plays a crucial role in amoebic invasion by triggering an array of cellular responses in the parasite, including induction of actin rich adhesion structures. Similar actin rich protrusive structures, known as 'invadosomes', promote chemotactic migration of the metastatic cancer cells and non-transformed cells by remodeling the ECM. Recent studies showed a central role for Rab GTPases, the master regulators of vesicular trafficking, in biogenesis of invadosomes. Here, we showed that fibronectin, a major host ECM component induced actin remodeling in the parasite in a Rab21 dependent manner. The focalized actin structures formed were reminiscent of the mammalian invadosomes. By using various approaches, such as immunofluorescence confocal microscopy and scanning electron microscopy, along with in vitro invasion assay and matrix degradation assay, we show that the fibronectin induced formation of amoebic actin dots depend on the nucleotide status of the GTPase. The ECM components, fibronectin and collagen type I, displayed differential control over the formation of actin dots, with fibronectin positively and collagen type I negatively modulating it. The cell surface adhesion molecule Gal/GalNAc complex was also found to impose additional regulation on this process, which might have implication in collagen type I mediated suppression of actin dots.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Entamoeba histolytica* / enzymology
  • Entamoeba histolytica* / genetics
  • Entamoeba histolytica* / pathogenicity
  • Fibronectins / metabolism*
  • Protozoan Proteins* / genetics
  • Protozoan Proteins* / metabolism
  • Trophozoites / enzymology
  • rab GTP-Binding Proteins* / genetics
  • rab GTP-Binding Proteins* / metabolism

Substances

  • Actins
  • Fibronectins
  • Protozoan Proteins
  • rab GTP-Binding Proteins

Grant support

The current study was supported from funds from Department of Science and Technology (DST), India, Japan Society for Promotion of Science (JSPS), Japan; Max Planck Gesellschaft (MPG) Germany; and Indian Institute of Science Education and Research Bhopal (IISERB), India. ME was supported from University Grants Commission Senior Research Fellowship, Govt. of India. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.