title: The 14-3-3 proteins of Trypanosoma brucei function in motility, cytokinesis, and cell cycle.
abstract: The cDNAs for two isoforms (I and II) of the 14-3-3 proteins have been cloned and functionally characterized in Trypanosoma brucei. The amino acid sequences of isoforms I and II have 47 and 50% identity to the human tau isoform, respectively, with important conserved features including a potential amphipathic groove for the binding of phosphoserine/phosphothreonine-containing motifs and a nuclear export signal-like domain. Both isoforms are abundantly expressed at approximately equal levels (1-2 x 10(6) molecules/cell) and localized mainly in the cytoplasm. Knockdown by induction of double-stranded RNA of isoform I and/or II in both bloodstream and procyclic forms resulted first in a reduction of cell motility and then significant reduction in cell growth rates and morphological changes; the changes include aberrant numbers of organelles and abnormal shapes and sizes that mimic phenotypes produced by various cytokinesis inhibitors. Morphological and fluorescence-activated cell sorting analysis of the cell cycle suggested that isoforms I and II might play important roles in nuclear (G2-M transition) and cell (M-G1 transition) division. These findings indicate that the 14-3-3 proteins play important roles in cell motility, cytokinesis, and the cell cycle.
authors.affiliation: Department of Parasitology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. inouedna@med.kurume-u.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inoue
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kouichi
authors.initials: K
authors.lastname: Yasuda
authors.forename: Natsumi
authors.initials: N
authors.lastname: Yasaka
authors.forename: Tatsuru
authors.initials: T
authors.lastname: Hara
authors.forename: Achim
authors.initials: A
authors.lastname: Schnaufer
authors.forename: Kenneth
authors.initials: K
authors.lastname: Stuart
authors.forename: Toshihide
authors.initials: T
authors.lastname: Fukuma
mesh_terms: D048948:14-3-3 Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D048430:Cell Shape; D048749:Cytokinesis / Q000502:physiology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014346:Trypanosoma brucei brucei / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D020033:Protein Isoforms; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases