LAMP-2 absence interferes with plasma membrane repair and decreases T. cruzi host cell invasion.
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 h...
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ftdoajarticles:oai:doaj.org/article:80a7b37153394f6ba7927785a6f5f0e0 2023-05-15T15:12:30+02:00 LAMP-2 absence interferes with plasma membrane repair and decreases T. cruzi host cell invasion. Natália Fernanda Couto Dina Pedersane Luisa Rezende Patrícia P Dias Tayanne L Corbani Lívia C Bentini Anny C S Oliveira Ludmila F Kelles Thiago Castro-Gomes Luciana O Andrade 2017-06-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0005657 https://doaj.org/article/80a7b37153394f6ba7927785a6f5f0e0 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5473579?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005657 https://doaj.org/article/80a7b37153394f6ba7927785a6f5f0e0 PLoS Neglected Tropical Diseases, Vol 11, Iss 6, p e0005657 (2017) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2017 ftdoajarticles https://doi.org/10.1371/journal.pntd.0005657 2022-12-31T06:35:59Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 11 6 e0005657 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Natália Fernanda Couto Dina Pedersane Luisa Rezende Patrícia P Dias Tayanne L Corbani Lívia C Bentini Anny C S Oliveira Ludmila F Kelles Thiago Castro-Gomes Luciana O Andrade LAMP-2 absence interferes with plasma membrane repair and decreases T. cruzi host cell invasion. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Natália Fernanda Couto Dina Pedersane Luisa Rezende Patrícia P Dias Tayanne L Corbani Lívia C Bentini Anny C S Oliveira Ludmila F Kelles Thiago Castro-Gomes Luciana O Andrade |
author_facet |
Natália Fernanda Couto Dina Pedersane Luisa Rezende Patrícia P Dias Tayanne L Corbani Lívia C Bentini Anny C S Oliveira Ludmila F Kelles Thiago Castro-Gomes Luciana O Andrade |
author_sort |
Natália Fernanda Couto |
title |
LAMP-2 absence interferes with plasma membrane repair and decreases T. cruzi host cell invasion. |
title_short |
LAMP-2 absence interferes with plasma membrane repair and decreases T. cruzi host cell invasion. |
title_full |
LAMP-2 absence interferes with plasma membrane repair and decreases T. cruzi host cell invasion. |
title_fullStr |
LAMP-2 absence interferes with plasma membrane repair and decreases T. cruzi host cell invasion. |
title_full_unstemmed |
LAMP-2 absence interferes with plasma membrane repair and decreases T. cruzi host cell invasion. |
title_sort |
lamp-2 absence interferes with plasma membrane repair and decreases t. cruzi host cell invasion. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2017 |
url |
https://doi.org/10.1371/journal.pntd.0005657 https://doaj.org/article/80a7b37153394f6ba7927785a6f5f0e0 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 11, Iss 6, p e0005657 (2017) |
op_relation |
http://europepmc.org/articles/PMC5473579?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005657 https://doaj.org/article/80a7b37153394f6ba7927785a6f5f0e0 |
op_doi |
https://doi.org/10.1371/journal.pntd.0005657 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
11 |
container_issue |
6 |
container_start_page |
e0005657 |
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1766343165162291200 |