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An orphan kinesin controls trypanosome morphology transitions by targeting FLAM3 to the flagellum
- Source :
- PLoS Pathogens, PLoS Pathogens, Vol 14, Iss 5, p e1007101 (2018)
- Publication Year :
- 2017
-
Abstract
- Trypanosoma brucei undergoes life cycle form transitions from trypomastigotes to epimastigotes in the insect vector by re-positioning the mitochondrial genome and re-locating the flagellum and flagellum-associated cytoskeletal structures. The mechanism underlying these dramatic morphology transitions remains poorly understood. Here we report the regulatory role of the orphan kinesin KIN-E in controlling trypanosome morphology transitions. KIN-E localizes to the flagellum and is enriched at the flagellar tip, and this localization depends on the C-terminal m-calpain domain III-like domains. Depletion of KIN-E in the trypomastigote form of T. brucei causes major morphology changes and a gradual increase in the level of EP procyclin, generating epimastigote-like cells. Mechanistically, through its C-terminal importin α-like domain, KIN-E targets FLAM3, a flagellar protein involved in morphology transitions, to the flagellum to promote elongation of the flagellum attachment zone and positioning of the flagellum and flagellum-associated cytoskeletal structure, thereby maintaining trypomastigote cell morphology. Our findings suggest that morphology transitions in trypanosomes require KIN-E-mediated transport of FLAM3 to the flagellum.<br />Author summary Trypanosoma brucei, the causative agent of sleeping sickness in humans and nagana in cattle in sub-Saharan Africa, has a complex life cycle by alternating between the tsetse fly vector and the mammalian hosts. In the gut of tsetse flies, trypanosomes undergo life cycle transitions from the trypomastigote form to the epimastigote form by re-positioning the mitochondrial genome and re-locating the flagellum and flagellum-associated cytoskeletal structures. Previous work demonstrated that elongation of the flagellum attachment zone plays an important role in controlling morphology transitions, but how it is regulated remains poorly understood. This work discovered that an orphan kinesin plays an essential role in regulating trypanosome morphology transitions. This novel kinesin localizes to the flagellum and targets FLAM3, one of the two flagellar proteins involved in morphology transitions, to the flagellum. This work suggests that trypanosome morphology transitions require kinesin-mediated transport of FLAM3 to the flagellum to promote the elongation of the flagellum attachment zone, thereby maintaining flagellum-cell body attachment and positioning the flagellum and flagellum-associated cytoskeletal structures to assume trypomastigote cell morphology.
- Subjects :
- 0301 basic medicine
Transcription Elongation, Genetic
Protozoan Proteins
Kinesins
Cell morphology
Pathology and Laboratory Medicine
Biochemistry
Protein Structure, Secondary
RNA interference
Medicine and Health Sciences
Cytoskeleton
Procyclin
lcsh:QH301-705.5
Protozoans
Membrane Glycoproteins
biology
Chemistry
musculoskeletal, neural, and ocular physiology
Microtubule Motors
Eukaryota
Cell biology
Precipitation Techniques
Nucleic acids
Genetic interference
Flagella
Kinesin
Epigenetics
Cellular Structures and Organelles
Pathogens
Research Article
lcsh:Immunologic diseases. Allergy
Pathogen Motility
Trypanosoma
Virulence Factors
Immunology
Trypanosoma brucei brucei
Importin
Trypanosoma brucei
Flagellum
Research and Analysis Methods
Microbiology
03 medical and health sciences
Molecular Motors
Virology
Genetics
Trypanosoma Brucei
Immunoprecipitation
Amino Acid Sequence
Molecular Biology
urogenital system
Organisms
Biology and Life Sciences
Proteins
Cell Biology
biochemical phenomena, metabolism, and nutrition
biology.organism_classification
Parasitic Protozoans
Cytoskeletal Proteins
030104 developmental biology
Kinetoplasts
lcsh:Biology (General)
bacteria
RNA
Parasitology
Gene expression
lcsh:RC581-607
Carrier Proteins
Sequence Alignment
Trypanosoma Brucei Gambiense
Subjects
Details
- ISSN :
- 15537374
- Volume :
- 14
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PLoS pathogens
- Accession number :
- edsair.doi.dedup.....38c53f1935c97209a1e047859699bf8a