title: Toxoplasma gondii Rab6 mediates a retrograde pathway for sorting of constitutively secreted proteins to the Golgi complex.
abstract: Toxoplasma gondii relies on protein secretion from specialized organelles for invasion of host cells and establishment of a parasitophorous vacuole. We identify T. gondii Rab6 as a regulator of protein transport between post-Golgi dense granule organelles and the Golgi. Toxoplasma Rab6 was localized to cisternal rims of the late Golgi and trans-Golgi network, associated transport vesicles, and microdomains of dense granule and endosomal membranes. Overexpression of wild-type Rab6 or GTP-activated Rab6(Q70L) rerouted soluble dense granule secretory proteins to the Golgi and endoplasmic reticulum and augmented the effect of brefeldin A on Golgi resorption to the endoplasmic reticulum. Parasites expressing a nucleotide-free (Rab6(N124I)) or a GDP-bound (Rab6(T25N)) mutant accumulated dense granule proteins in the Golgi and associated transport vesicles and displayed reduced secretion of GRA4 and a delay in glycosylation of GRA2. Activated Rab6 on Golgi membranes colocalized with centrin during mitosis, and parasite clones expressing Rab6 mutants displayed a partial shift in cytokinesis from endodyogeny (formation of two daughter cells) to endopolygeny (multiple daughter cells). We propose that Toxoplasma Rab6 regulates retrograde transport from post-Golgi secretory granules to the parasite Golgi.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8022, USA. Stedman@biomed.med.yale.edu
authors.forename: Timothy T
authors.initials: TT
authors.lastname: Stedman
authors.forename: A Ross
authors.initials: AR
authors.lastname: Sussmann
authors.forename: Keith A
authors.initials: KA
authors.lastname: Joiner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006056:Golgi Apparatus / Q000502:physiology; D008969:Molecular Sequence Data; D021381:Protein Transport / Q000502:physiology*; D015800:Protozoan Proteins / Q000502:physiology; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D014122:Toxoplasma / Q000502:physiology* / Q000648:ultrastructure; D020691:rab GTP-Binding Proteins / Q000502:physiology*
chemical_list: D015800:Protozoan Proteins; C094135:Rab6 protein; D020691:rab GTP-Binding Proteins