title: KHARON Is an Essential Cytoskeletal Protein Involved in the Trafficking of Flagellar Membrane Proteins and Cell Division in African Trypanosomes.
abstract: African trypanosomes and related kinetoplastid parasites selectively traffic specific membrane proteins to the flagellar membrane, but the mechanisms for this trafficking are poorly understood. We show here that KHARON, a protein originally identified in Leishmania parasites, interacts with a putative trypanosome calcium channel and is required for its targeting to the flagellar membrane. KHARON is located at the base of the flagellar axoneme, where it likely mediates targeting of flagellar membrane proteins, but is also on the subpellicular microtubules and the mitotic spindle. Hence, KHARON is probably a multifunctional protein that associates with several components of the trypanosome cytoskeleton. RNA interference-mediated knockdown of KHARON mRNA results in failure of the calcium channel to enter the flagellar membrane, detachment of the flagellum from the cell body, and disruption of mitotic spindles. Furthermore, knockdown of KHARON mRNA induces a lethal failure of cytokinesis in both bloodstream (mammalian host) and procyclic (insect vector) life cycle stages, and KHARON is thus critical for parasite viability.
authors.affiliation: From the Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon 97239 and.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Sanchez
authors.affiliation: From the Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon 97239 and.
authors.forename: Khoa D
authors.initials: KD
authors.lastname: Tran
authors.affiliation: the Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
authors.forename: Jessica
authors.initials: J
authors.lastname: Valli
authors.affiliation: From the Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon 97239 and.
authors.forename: Sam
authors.initials: S
authors.lastname: Hobbs
authors.affiliation: the Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
authors.forename: Errin
authors.initials: E
authors.lastname: Johnson
authors.affiliation: the Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
authors.forename: Eva
authors.initials: E
authors.lastname: Gluenz
authors.affiliation: From the Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon 97239 and landfear@ohsu.edu.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Landfear
mesh_terms: D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D048749:Cytokinesis / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005407:Flagella / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D007891:Leishmania / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D003598:Cytoskeletal Proteins; D015800:Protozoan Proteins
keywords: Trypanosoma brucei; calcium channel; cytoskeleton; membrane protein; mitotic spindle; trafficking