title: Chemotaxis of Entamoeba histolytica towards the pro-inflammatory cytokine TNF is based on PI3K signalling, cytoskeleton reorganization and the Galactose/N-acetylgalactosamine lectin activity.
abstract: Entamoeba histolytica is the protozoan parasite responsible for human amoebiasis. During invasive amoebiasis, migration is an essential process and it has previously been shown that the pro-inflammatory compound tumour necrosis factor (TNF) is produced and that it has a migratory effect on E. histolytica. This paper focuses on the analysis of parasite signalling and cytoskeleton changes leading to directional motility. TNF-induced signalling was PI3K-dependent and could lead to modifications in the polarization of certain cytoskeleton-related proteins. To analyse the effect of TNF signalling on gene expression, we used microarray analysis to screen for genes encoding proteins that were potentially important during chemotaxis towards TNF. Interestingly, we found that elements of the galactose/N-acetylgalactosamine lectin (Gal/GalNAc lectin) were upregulated during chemotaxis as well as genes encoding proteins involved in cytoskeleton dynamics. The alpha-actinin protein appeared to be an important candidate to link the Gal/GalNAc lectin to the cytoskeleton during chemotaxis signalling. Dominant negative parasites blocked for Gal/GalNAc lectin signalling were no longer able to chemotax towards TNF. These results have given us an insight on how E. histolytica changes its cytoskeleton dynamics during chemotaxis and revealed the capital role of PI3K and Gal/GalNAc lectin signalling in chemotaxis.
authors.affiliation: Institut Pasteur, Unité de Biologie Cellulaire du Parasitisme, Paris, F-75015, France.
authors.forename: Samantha
authors.initials: S
authors.lastname: Blazquez
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Guigon
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: Sylvie
authors.initials: S
authors.lastname: Syan
authors.forename: Odile
authors.initials: O
authors.lastname: Sismeiro
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Coppée
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Labruyère
authors.forename: Nancy
authors.initials: N
authors.lastname: Guillén
mesh_terms: D000116:Acetylgalactosamine / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002633:Chemotaxis; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D004748:Entamoeba histolytica / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D005690:Galactose / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D037102:Lectins / Q000276:immunology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015800:Protozoan Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D048069:Tumor Necrosis Factors / Q000276:immunology*; D000077191:Wortmannin
chemical_list: D000116:Acetylgalactosamine; D000730:Androstadienes; D005690:Galactose; D037102:Lectins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015800:Protozoan Proteins; D048069:Tumor Necrosis Factors; D000077191:Wortmannin