Toxoplasma gondii Rab6 mediates a retrograde pathway for sorting of constitutively secreted proteins to the Golgi complex

Timothy T. Stedman, A. Ross Sussmann, Keith A Joiner

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 wildtype 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.

Original languageEnglish (US)
Pages (from-to)5433-5443
Number of pages11
JournalJournal of Biological Chemistry
Volume278
Issue number7
DOIs
StatePublished - Feb 14 2003
Externally publishedYes

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Toxoplasma
Golgi Apparatus
Sorting
Transport Vesicles
Parasites
Secretory Vesicles
Endoplasmic Reticulum
Organelles
Proteins
Glycosylation
Membranes
trans-Golgi Network
Brefeldin A
Cytokinesis
Sulfamethoxazole Drug Combination Trimethoprim
Protein Transport
Vacuoles
Guanosine Triphosphate
Mitosis
Nucleotides

ASJC Scopus subject areas

  • Biochemistry

Cite this

Toxoplasma gondii Rab6 mediates a retrograde pathway for sorting of constitutively secreted proteins to the Golgi complex. / Stedman, Timothy T.; Sussmann, A. Ross; Joiner, Keith A.

In: Journal of Biological Chemistry, Vol. 278, No. 7, 14.02.2003, p. 5433-5443.

Research output: Contribution to journalArticle

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