title: Protein kinase involved in flagellar-length control.
abstract: During its life cycle, the parasitic protozoon Leishmania mexicana differentiates from a flagellated form, the promastigote, to an amastigote form carrying a rudimentary flagellum. Besides biochemical changes, this process involves a change in overall cell morphology including flagellar shortening. A mitogen-activated protein kinase kinase homologue designated LmxMKK was identified in a homology screening and found to be critically involved in the regulation of flagellar assembly and cell size. LmxMKK is exclusively expressed in the promastigote stage and is likely to be regulated by posttranslational mechanisms such as phosphorylation. A deletion mutant for the single-copy gene revealed motile flagella dramatically reduced in length and lacking the paraflagellar rod, a structure adjacent to the axoneme in kinetoplastid flagella. Moreover, a fraction of the cells showed perturbance of the axonemal structure. Complementation of the deletion mutant with the wild-type gene restored typical promastigote morphology. We propose that LmxMKK influences anterograde intraflagellar transport to maintain flagellar length in Leishmania promastigotes; as such, it is the first protein kinase known to be involved in organellar assembly.
authors.affiliation: Parasitology Section, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany. martin.wiese@bni-hamburg.de
authors.forename: Martin
authors.initials: M
authors.lastname: Wiese
authors.forename: Daniela
authors.initials: D
authors.lastname: Kuhn
authors.forename: Christoph G
authors.initials: CG
authors.lastname: Grünfelder
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D048429:Cell Size / Q000235:genetics; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D005407:Flagella / Q000201:enzymology* / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000235:genetics; D007894:Leishmania mexicana / Q000201:enzymology* / Q000648:ultrastructure; D051379:Mice; D008854:Microscopy, Electron; D020929:Mitogen-Activated Protein Kinase Kinases / Q000172:deficiency* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D018076:DNA, Complementary; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D020929:Mitogen-Activated Protein Kinase Kinases