Small GTPase Rab21 Mediates Fibronectin Induced Actin Reorganization in Entamoeba histolytica: Implications in Pathogen Invasion

PLoS Pathogens

Merlyn Emmanuel¹  Sunando Datta¹  Yumiko Saito Nakano²  Tomoyoshi Nozaki² 

[1] Department of Biological Sciences, Indian Institute of Science Education and Research Bhopal, Bhopal, India;Department of Parasitology, National Institute of Infectious Diseases, Tokyo, Japan

关键词: Actins;    Trophozoites;    Collagens;    Extracellular matrix;    Entamoeba histolytica;    Glass;    Guanosine triphosphatase;    Cytoskeleton;   

DOI  :  10.1371/journal.ppat.1004666

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY