The kinesin of the flagellum attachment zone in Leishmania is required for cell morphogenesis, cell division and virulence in the mammalian host.
Leishmania parasites possess a unique and complex cytoskeletal structure termed flagellum attachment zone (FAZ) connecting the base of the flagellum to one side of the flagellar pocket (FP), an invagination of the cell body membrane and the sole site for endocytosis and exocytosis. This structure is...
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2021-06-01
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doaj-0f2c6b9c7f12491a96936e7b139ee1552021-07-16T04:32:09ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-06-01176e100966610.1371/journal.ppat.1009666The kinesin of the flagellum attachment zone in Leishmania is required for cell morphogenesis, cell division and virulence in the mammalian host.Rosa Milagros CorralesSlavica VaselekRachel NeishLaurence BerryCamille D BrunetLucien CrobuNada KukJulio Mateos-LangerakDerrick R RobinsonPetr VolfJeremy C MottramYvon SterkersPatrick BastienLeishmania parasites possess a unique and complex cytoskeletal structure termed flagellum attachment zone (FAZ) connecting the base of the flagellum to one side of the flagellar pocket (FP), an invagination of the cell body membrane and the sole site for endocytosis and exocytosis. This structure is involved in FP architecture and cell morphogenesis, but its precise role and molecular composition remain enigmatic. Here, we characterized Leishmania FAZ7, the only known FAZ protein containing a kinesin motor domain, and part of a clade of trypanosomatid-specific kinesins with unknown functions. The two paralogs of FAZ7, FAZ7A and FAZ7B, display different localizations and functions. FAZ7A localizes at the basal body, while FAZ7B localizes at the distal part of the FP, where the FAZ structure is present in Leishmania. While null mutants of FAZ7A displayed normal growth rates, the deletion of FAZ7B impaired cell growth in both promastigotes and amastigotes of Leishmania. The kinesin activity is crucial for its function. Deletion of FAZ7B resulted in altered cell division, cell morphogenesis (including flagellum length), and FP structure and function. Furthermore, knocking out FAZ7B induced a mis-localization of two of the FAZ proteins, and disrupted the molecular organization of the FP collar, affecting the localization of its components. Loss of the kinesin FAZ7B has important consequences in the insect vector and mammalian host by reducing proliferation in the sand fly and pathogenicity in mice. Our findings reveal the pivotal role of the only FAZ kinesin as part of the factors important for a successful life cycle of Leishmania.https://doi.org/10.1371/journal.ppat.1009666 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rosa Milagros Corrales Slavica Vaselek Rachel Neish Laurence Berry Camille D Brunet Lucien Crobu Nada Kuk Julio Mateos-Langerak Derrick R Robinson Petr Volf Jeremy C Mottram Yvon Sterkers Patrick Bastien |
spellingShingle |
Rosa Milagros Corrales Slavica Vaselek Rachel Neish Laurence Berry Camille D Brunet Lucien Crobu Nada Kuk Julio Mateos-Langerak Derrick R Robinson Petr Volf Jeremy C Mottram Yvon Sterkers Patrick Bastien The kinesin of the flagellum attachment zone in Leishmania is required for cell morphogenesis, cell division and virulence in the mammalian host. PLoS Pathogens |
author_facet |
Rosa Milagros Corrales Slavica Vaselek Rachel Neish Laurence Berry Camille D Brunet Lucien Crobu Nada Kuk Julio Mateos-Langerak Derrick R Robinson Petr Volf Jeremy C Mottram Yvon Sterkers Patrick Bastien |
author_sort |
Rosa Milagros Corrales |
title |
The kinesin of the flagellum attachment zone in Leishmania is required for cell morphogenesis, cell division and virulence in the mammalian host. |
title_short |
The kinesin of the flagellum attachment zone in Leishmania is required for cell morphogenesis, cell division and virulence in the mammalian host. |
title_full |
The kinesin of the flagellum attachment zone in Leishmania is required for cell morphogenesis, cell division and virulence in the mammalian host. |
title_fullStr |
The kinesin of the flagellum attachment zone in Leishmania is required for cell morphogenesis, cell division and virulence in the mammalian host. |
title_full_unstemmed |
The kinesin of the flagellum attachment zone in Leishmania is required for cell morphogenesis, cell division and virulence in the mammalian host. |
title_sort |
kinesin of the flagellum attachment zone in leishmania is required for cell morphogenesis, cell division and virulence in the mammalian host. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2021-06-01 |
description |
Leishmania parasites possess a unique and complex cytoskeletal structure termed flagellum attachment zone (FAZ) connecting the base of the flagellum to one side of the flagellar pocket (FP), an invagination of the cell body membrane and the sole site for endocytosis and exocytosis. This structure is involved in FP architecture and cell morphogenesis, but its precise role and molecular composition remain enigmatic. Here, we characterized Leishmania FAZ7, the only known FAZ protein containing a kinesin motor domain, and part of a clade of trypanosomatid-specific kinesins with unknown functions. The two paralogs of FAZ7, FAZ7A and FAZ7B, display different localizations and functions. FAZ7A localizes at the basal body, while FAZ7B localizes at the distal part of the FP, where the FAZ structure is present in Leishmania. While null mutants of FAZ7A displayed normal growth rates, the deletion of FAZ7B impaired cell growth in both promastigotes and amastigotes of Leishmania. The kinesin activity is crucial for its function. Deletion of FAZ7B resulted in altered cell division, cell morphogenesis (including flagellum length), and FP structure and function. Furthermore, knocking out FAZ7B induced a mis-localization of two of the FAZ proteins, and disrupted the molecular organization of the FP collar, affecting the localization of its components. Loss of the kinesin FAZ7B has important consequences in the insect vector and mammalian host by reducing proliferation in the sand fly and pathogenicity in mice. Our findings reveal the pivotal role of the only FAZ kinesin as part of the factors important for a successful life cycle of Leishmania. |
url |
https://doi.org/10.1371/journal.ppat.1009666 |
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