title: Host Epac1 is required for cAMP-mediated invasion by Trypanosoma cruzi.
abstract: Mechanistic details of the modulation by cAMP of Trypanosoma cruzi host cell invasion remain ill-defined. Here we report that activation of host's Epac1 stimulated invasion, whereas specific pharmacological inhibition or maneuvers that alter Epac1 subcellular localization significantly reduced invasion. Furthermore, while specific activation of host cell PKA showed no effect, its inhibition resulted in an increased invasion, revealing a crosstalk between the PKA and Epac signaling pathways during the process of invasion. Therefore, our data suggests that subcellular localization of Epac might be playing an important role during invasion and that specific activation of the host cell cAMP/Epac1 pathway is required for cAMP-mediated invasion.
authors.affiliation: IQUIBICEN-CONICET-Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina.
authors.forename: Daniel
authors.initials: D
authors.lastname: Musikant
authors.affiliation: IQUIBICEN-CONICET-Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Ferri
authors.affiliation: Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús, UNSAM-CONICET, Buenos Aires, Argentina.
authors.forename: Ignacio M
authors.initials: IM
authors.lastname: Durante
authors.affiliation: Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús, UNSAM-CONICET, Buenos Aires, Argentina.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Buscaglia
authors.affiliation: Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: altschul@pitt.edu.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Altschuler
authors.affiliation: IQUIBICEN-CONICET-Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina; Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: mme2@pitt.edu.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Edreira
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006790:Host-Parasite Interactions; D021381:Protein Transport; D051381:Rats; D015398:Signal Transduction; D014349:Trypanosoma cruzi / Q000472:pathogenicity / Q000502:physiology*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C526973:Rapgef3 protein, rat; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Epac; Invasion; PKA; Trypanosoma cruzi; cAMP