title: Trypanosoma cruzi extracellular amastigotes trigger the protein kinase D1-cortactin-actin pathway during cell invasion.
abstract: Trypanosoma cruzi extracellular amastigotes (EAs) display unique mechanisms for cell invasion that are highly dependent on host actin filaments. Protein kinase D1 (PKD1) phosphorylates and modulates the activity of cortactin, a key regulator of actin dynamics. We evaluated the role of host cortactin and PKD1 in actin filament dynamics during HeLa cell invasion by EAs. Host cortactin, PKD1 and actin are recruited by EAs based on experiments in fixed and live cells by time lapse confocal microscopy. EAs trigger PKD1 and extracellular signal-regulated kinase 1/2 activation, but not Src family kinases, and selectively phosphorylate cortactin. Heat-killed EAs and non-infective epimastigotes both triggered distinct host responses and did not recruit the molecules studied herein. EA invasion was influenced by depletion or overexpression of host cortactin and PKD1, respectively, suggesting the involvement of both proteins in this event. Collectively, these results show new host cell mechanisms subverted during EA internalization into non-phagocytic cells.
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM-UNIFESP), São Paulo, Brazil.
authors.forename: Alexis
authors.initials: A
authors.lastname: Bonfim-Melo
authors.affiliation: Interdisciplinary Center for Gene Therapy (CINTERGEN), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Bianca Ferrarini
authors.initials: BF
authors.lastname: Zanetti
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM-UNIFESP), São Paulo, Brazil.
authors.forename: Éden Ramalho
authors.initials: ÉR
authors.lastname: Ferreira
authors.affiliation: Department of Cellular and Molecular Medicine, University of Leuven, Leuven, Belgium.
authors.forename: Sandy
authors.initials: S
authors.lastname: Vandoninck
authors.affiliation: Interdisciplinary Center for Gene Therapy (CINTERGEN), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Han
authors.affiliation: Department of Cellular and Molecular Medicine, University of Leuven, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Van Lint
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM-UNIFESP), São Paulo, Brazil.
authors.forename: Renato Arruda
authors.initials: RA
authors.lastname: Mortara
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (EPM-UNIFESP), São Paulo, Brazil.|Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (ICB-UFMG), Belo Horizonte, Brazil.
authors.forename: Diana
authors.initials: D
authors.lastname: Bahia
mesh_terms: D000199:Actins / Q000378:metabolism*; D051356:Cortactin / Q000378:metabolism*; D004705:Endocytosis; D004847:Epithelial Cells / Q000469:parasitology / Q000502:physiology; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D018613:Microscopy, Confocal; D011493:Protein Kinase C / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D059008:Time-Lapse Imaging; D014349:Trypanosoma cruzi / Q000502:physiology*
chemical_list: D000199:Actins; D051356:Cortactin; C089212:protein kinase D; D011493:Protein Kinase C