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LAMP-2 absence interferes with plasma membrane repair and decreases T. cruzi host cell invasion.
Couto, Natália Fernanda; Pedersane, Dina; Rezende, Luisa; Dias, Patrícia P; Corbani, Tayanne L; Bentini, Lívia C; Oliveira, Anny C S; Kelles, Ludmila F; Castro-Gomes, Thiago; Andrade, Luciana O.
Afiliação
  • Couto NF; Department of Morphology/Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
  • Pedersane D; Department of Morphology/Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
  • Rezende L; Department of Morphology/Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
  • Dias PP; Department of Morphology/Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
  • Corbani TL; Department of Morphology/Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
  • Bentini LC; Department of Morphology/Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
  • Oliveira ACS; Department of Morphology/Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
  • Kelles LF; Department of Morphology/Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
  • Castro-Gomes T; Department of Biochemistry and Immunology/Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
  • Andrade LO; Department of Morphology/Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
PLoS Negl Trop Dis ; 11(6): e0005657, 2017 Jun.
Article em En | MEDLINE | ID: mdl-28586379
Trypanosoma cruzi enters host cells by subverting the mechanism of cell membrane repair. In this process, the parasite induces small injuries in the host cell membrane leading to calcium entry and lysosomal exocytosis, which are followed by compensatory endocytosis events that drive parasites into host cells. We have previously shown that absence of both LAMP-1 and 2, major components of lysosomal membranes, decreases invasion of T. cruzi into host cells, but the mechanism by which they interfere with parasite invasion has not been described. Here we investigated the role of these proteins in parasitophorous vacuole morphology, host cell lysosomal exocytosis, and membrane repair ability. First, we showed that cells lacking only LAMP-2 present the same invasion phenotype as LAMP1/2-/- cells, indicating that LAMP-2 is an important player during T. cruzi invasion process. Second, neither vacuole morphology nor lysosomal exocytosis was altered in LAMP-2 lacking cells (LAMP2-/- and LAMP1/2-/- cells). We then investigated the ability of LAMP-2 deficient cells to perform compensatory endocytosis upon lysosomal secretion, the mechanism by which cells repair their membrane and T. cruzi ultimately enters cells. We observed that these cells perform less endocytosis upon injury when compared to WT cells. This was a consequence of impaired cholesterol traffic in cells lacking LAMP-2 and its influence in the distribution of caveolin-1 at the cell plasma membrane, which is crucial for plasma membrane repair. The results presented here show the major role of LAMP-2 in caveolin traffic and membrane repair and consequently in T. cruzi invasion.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trypanosoma cruzi / Membrana Celular / Proteínas de Membrana Lisossomal / Proteína 2 de Membrana Associada ao Lisossomo / Fibroblastos Limite: Animals Idioma: En Revista: PLoS Negl Trop Dis Assunto da revista: MEDICINA TROPICAL Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trypanosoma cruzi / Membrana Celular / Proteínas de Membrana Lisossomal / Proteína 2 de Membrana Associada ao Lisossomo / Fibroblastos Limite: Animals Idioma: En Revista: PLoS Negl Trop Dis Assunto da revista: MEDICINA TROPICAL Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos