The kinesin of the flagellum attachment zone in Leishmania is required for cell morphogenesis, cell division and virulence in the mammalian host.
| Title: | The kinesin of the flagellum attachment zone in Leishmania is required for cell morphogenesis, cell division and virulence in the mammalian host. |
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| Authors: | Corrales RM; Research Unit 'MiVEGEC', University of Montpellier, CNRS, IRD, Academic Hospital (CHU) of Montpellier, Montpellier, France.; Vaselek S; Department of Parasitology, Charles University, Prague, Czech Republic.; Neish R; York Biomedical Research Institute and Department of Biology, University of York, York, United Kingdom.; Berry L; Research Unit 'LPHI' (Laboratory of Pathogen Host Interactions), University of Montpellier, CNRS, Montpellier, France.; Brunet CD; Research Unit 'MiVEGEC', University of Montpellier, CNRS, IRD, Academic Hospital (CHU) of Montpellier, Montpellier, France.; Crobu L; Research Unit 'MiVEGEC', University of Montpellier, CNRS, IRD, Academic Hospital (CHU) of Montpellier, Montpellier, France.; Kuk N; Research Unit 'MiVEGEC', University of Montpellier, CNRS, IRD, Academic Hospital (CHU) of Montpellier, Montpellier, France.; Mateos-Langerak J; Institut de Génétique Humaine, University of Montpellier, CNRS, Montpellier, France.; Robinson DR; Research Unit 'Fundamental Microbiology and Pathogenicity', 'Protist Parasite Cytoskeleton (ProParaCyto)', University of Bordeaux, UMR 5234, CNRS, Bordeaux, France.; Volf P; Department of Parasitology, Charles University, Prague, Czech Republic.; Mottram JC; York Biomedical Research Institute and Department of Biology, University of York, York, United Kingdom.; Sterkers Y; Research Unit 'MiVEGEC', University of Montpellier, CNRS, IRD, Academic Hospital (CHU) of Montpellier, Montpellier, France.; Bastien P; Research Unit 'MiVEGEC', University of Montpellier, CNRS, IRD, Academic Hospital (CHU) of Montpellier, Montpellier, France. |
| Source: | PLoS pathogens [PLoS Pathog] 2021 Jun 18; Vol. 17 (6), pp. e1009666. Date of Electronic Publication: 2021 Jun 18 (Print Publication: 2021). |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: San Francisco, CA : Public Library of Science, c2005- |
| MeSH Terms: | Flagella/*metabolism ; Kinesins/*metabolism ; Leishmania mexicana/*pathogenicity ; Leishmaniasis/*metabolism ; Virulence/*physiology; Leishmania mexicana/physiology ; Protozoan Proteins/metabolism ; Animals ; Cell Proliferation ; Mice ; Morphogenesis ; Psychodidae |
| Abstract: | 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. |
| Competing Interests: | The authors have declared that no competing interests exist. |
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| Grant Information: | United Kingdom WT_ Wellcome Trust; 200807/Z/16/Z United Kingdom WT_ Wellcome Trust |
| Substance Nomenclature: | 0 (Protozoan Proteins); EC 3.6.4.4 (Kinesins) |
| Entry Date(s): | Date Created: 20210618 Date Completed: 20211007 Latest Revision: 20211204 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC8244899 |
| DOI: | 10.1371/journal.ppat.1009666 |
| PMID: | 34143858 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't