The kinesin of the flagellum attachment zone in Leishmania is required for cell morphogenesis, cell division and virulence in the mammalian host
| Autor: | Rosa Milagros Corrales, Yvon Sterkers, Patrick Bastien, Julio Mateos-Langerak, Rachel Neish, Nada Kuk, Slavica Vaselek, Derrick R. Robinson, Laurence Berry, Jeremy C. Mottram, Lucien Crobu, Camille D. Brunet, Petr Volf |
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| Přispěvatelé: | Biologie, Génétique et Pathologie des Pathogènes Eucaryotes (MIVEGEC-BioGEPPE), Pathogènes, Environnement, Santé Humaine (EPATH), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Charles University [Prague] (CU), University of York [York, UK], LPHI - Laboratory of Pathogen Host Interactions (LPHI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut de génétique humaine (IGH), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Laboratory of Pathogen Host Interactions [Montpellier] (LPHI), Microbiologie Fondamentale et Pathogénicité (MFP), ANR-19-CE17-0014,FLAGEL-OME,Aspects fondamentaux, génétiques et cliniques de l'infertilité masculine causée par des anomalies sévères des flagelles spermatiques(2019), ANR-20-CE91-0003,Structu-Ring,Pourquoi et comment les trypanosomes construisent un Collier de la Poche Flagellaire(2020) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Life Cycles
Cell division Leishmania mexicana Protozoan Proteins Kinesins [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] Protozoology Pathology and Laboratory Medicine Biochemistry Mice Medical Conditions Medicine and Health Sciences Morphogenesis Basal body Cell Cycle and Cell Division Biology (General) Cell body membrane Cytoskeleton Leishmaniasis Protozoans Leishmania 0303 health sciences Virulence 030302 biochemistry & molecular biology Microtubule Motors Eukaryota Cell biology Flagella Cell Processes Kinesin Protozoan Life Cycles Cellular Structures and Organelles Pathogens Research Article Amastigotes Pathogen Motility QH301-705.5 Virulence Factors Immunology Motor Proteins Flagellum Biology Microbiology 03 medical and health sciences Molecular Motors Virology Genetics Parasitic Diseases Animals [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology Molecular Biology 030304 developmental biology Cell Proliferation Cell growth Cell morphogenesis Promastigotes Organisms Biology and Life Sciences Proteins Cell Biology RC581-607 Parasitic Protozoans Cytoskeletal Proteins Parasitology Immunologic diseases. Allergy Psychodidae Developmental Biology |
| Zdroj: | PLoS Pathogens PLoS Pathogens, Public Library of Science, 2021, 17 (6), pp.e1009666. ⟨10.1371/journal.ppat.1009666⟩ PLoS Pathogens, 2021, 17 (6), pp.e1009666. ⟨10.1371/journal.ppat.1009666⟩ PLOS Pathogens PLoS Pathogens, Vol 17, Iss 6, p e1009666 (2021) |
| ISSN: | 1553-7366 1553-7374 |
| DOI: | 10.1371/journal.ppat.1009666⟩ |
| Popis: | 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. Author summary Leishmania are flagellated trypanosomatid parasites causing worldwide human and animal diseases. As ’divergent eukaryotes’, their biology presents unique features and structures, of which the specific functions constitute potential drug targets. Among others, they possess a unique cytoskeletal structure termed the flagellum attachment zone (FAZ) attaching the base of their flagellum to one side of the flagellar pocket (FP), which is the sole site for endocytosis and exocytosis. The FP together with other unique flagellum-associated structures are crucial for parasite survival, but the functioning of this whole remains largely enigmatic. Leishmania also possess an expanded repertoire of kinesins (>55), including two trypanosomatid-specific families. Here, we show that the deletion of the sole kinesin among FAZ proteins disrupts cell morphogenesis, FP organisation and cell division. Furthermore, the ability to proliferate in the insect vector and mammalian host is reduced in parasites lacking the kinesin FAZ7B. This study helps elucidate the factors contributing to the successful lifecycle and pathogenicity of the parasite. It also highlights the functional diversification of motor proteins during evolution. |
| Databáze: | OpenAIRE |
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