Lysosomal integral membrane protein 2 (LIMP-2) restricts the invasion of Trypanosoma cruzi extracellular amastigotes through the activity of the lysosomal enzyme beta-glucocerebrosidase

Lysosomal integral membrane protein 2 (LIMP-2) restricts the invasion of Trypanosoma cruzi extracellular amastigotes through the activity of the lysosomal enzyme beta-glucocerebrosidase

Author Goncalves, Viviane Martinelli Autor UNIFESP Google Scholar
D'Almeida, Vania Autor UNIFESP Google Scholar
Mueller, Karen Barbosa Autor UNIFESP Google Scholar
Real, Fernando Autor UNIFESP Google Scholar
Mortara, Renato Arruda Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract Lysosomal integral membrane protein 2 (LDM1P-2, SCARB2) is directly linked to beta-glucocerebrosidase enzyme (beta GC) and mediates the transport of this enzyme from the Golgi complex to lysosomes. Active beta GC cleaves the beta-glycosidic linkages of glucosylceramide, an intermediate in the metabolism of sphingoglycolipids, generating ceramide. in this study we used mouse embryonic fibroblasts (MEFs) deficient for LIMP-2 and observed that these cells were more susceptible to infection by extracellular amastigotes of the protozoan parasite Trypanosoma cruzi when compared to wild-type (WT) fibroblasts. the absence of LIMP-2 decreases the activity of beta GC measured in fibroblast extracts. Replacement of beta GC enzyme in LIMP-2 deficient fibroblasts restores the infectivity indices to those of WT cells in T cruzti invasion assays. Considering the participation of beta GC in the production of host cell ceramide, we propose that T cruzi extracellular amastigotes are more invasive to cells deficient in this membrane component. These results contribute to our understanding of the role of host cell lysosomal components in T cruzi invasion. (C) 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
Keywords LIMP-2
beta-Glucocerebrosidase
Trypanosoma cruzi
Extracellular amastigotes
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Grant number FAPESP: 10/19335-4
Date 2014-03-01
Published in Microbes and Infection. Amsterdam: Elsevier B.V., v. 16, n. 3, p. 253-260, 2014.
ISSN 1286-4579 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 253-260
Origin http://dx.doi.org/10.1016/j.micinf.2013.11.004
Access rights Closed access
Type Article
Web of Science ID WOS:000347864600010
URI http://repositorio.unifesp.br/handle/11600/37496

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