Trypanosoma cruzi extracellular amastigotes trigger the protein kinase D1-cortactin-actin pathway during cell invasion

Autor(es)

Bonfim-Melo, Alexis ^[1] ; Zanetti, Bianca Ferrarini ^[2] ; Ferreira, Eden Ramalho ^[1] ; Vandoninck, Sandy ^[3] ; Han, Sang Won ^[2] ; Van Lint, Johan ^[3] ; Mortara, Renato Arruda ^[1] ; Bahia, Diana ^{[4, 1]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, EPM UNIFESP, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo UNIFESP, Interdisciplinary Ctr Gene Therapy CINTERGEN, Sao Paulo - Brazil

^[3] Univ Leuven, Dept Cellular & Mol Med, Leuven - Belgium

^[4] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Biol Geral, Belo Horizonte, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Cellular Microbiology; v. 17, n. 12, p. 1797-1810, DEC 2015.
• Citações Web of Science: 9

Resumo

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. (AU)

• Processo FAPESP: 07/50551-2 - Identificação e caracterização molecular de proteínas quinases de Trypanosoma cruzi para o estudo da comunicação celular, modelagem molecular e desenho de drogas inibidoras: estudo dos parceiros das vias de sinalização focado na invasão de EA
• Beneficiário: Diana Bahia
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 10/14190-8 - Papel da proteína quinase D e cortactina na invasão celular por amastigotas extracelulares de Trypanosoma cruzi
• Beneficiário: Alexis de Sá Ribeiro do Bonfim de Melo
• Modalidade de apoio: Bolsas no Brasil - Mestrado