![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
A more recent version of this article appeared on July 1, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on January 14, 2002
Revised on March 25, 2002
Accepted on April 12, 2002
1 CNRS FRE 2383, Bâtiment CERMO, Université Joseph Fourier, Grenoble, France
2 CNRS UMR 5539, Université Montpellier II, Montpellier, France
3 Laboratory of Molecular Parasitology, Université Libre de Bruxelles, Gosselies, Belgium
4 Washington University School of Medicine, Department of Molecular Microbiology, Saint Louis, MO, USA
* Corresponding author. E-mail address: marie-france.cesbron{at}ujf-grenoble.fr.
The intracellular parasite Toxoplasma gondii develops within a non-fusogenic vacuole containing a network of elongated nanotubules that form connections with the vacuolar membrane. Parasite secretory proteins discharged from dense granules (known as GRA proteins) decorate this intravacuolar network following invasion. Here, we show using specific gene knock-out mutants, that the unique nanotubule conformation of the network is induced by the parasite secretory protein GRA2 and further stabilized by GRA6. The vacuolar compartment generated by GRA2 knock-out parasites was dramatically disorganized, and the normally tubular network was replaced by small aggregated material. The defect observed in ·gra2 parasites was evident from the initial stages of network formation when a prominent cluster of multilamellar vesicles forms at a posterior invagination of the parasite. The secretory protein GRA6 failed to localize properly to this posterior organizing center in 
gra2 cells, indicating that this early conformation is essential to proper assembly of the network. Construction of a gra6 mutant also led to an altered mature network characterized by small vesicles instead of elongated nanotubules; however, the initial formation of the posterior organizing center was normal. Complementation of the gra2 knock-out with mutated forms of GRA2 showed that the integrity of both amphipathic alpha-helices of the protein is required for correct formation of the network. The induction of nanotubues by the parasite protein GRA2 may be a conserved feature of amphipathic alpha-helical regions, which have also been implicated in the organization of Golgi nanotubules and endocytic vesicles in mammalian cells.
This article has been cited by other articles:
|
|
 |
|
  M. E. Rome, J. R. Beck, J. M. Turetzky, P. Webster, and P. J. Bradley Intervacuolar Transport and Unique Topology of GRA14, a Novel Dense Granule Protein in Toxoplasma gondii Infect. Immun., November 1, 2008; 76(11): 4865 - 4875. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Que, J. C. Engel, D. Ferguson, A. Wunderlich, S. Tomavo, and S. L. Reed Cathepsin Cs Are Key for the Intracellular Survival of the Protozoan Parasite, Toxoplasma gondii J. Biol. Chem., February 16, 2007; 282(7): 4994 - 5003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. W. Zhou, B. F. C. Kafsack, R. N. Cole, P. Beckett, R. F. Shen, and V. B. Carruthers The Opportunistic Pathogen Toxoplasma gondii Deploys a Diverse Legion of Invasion and Survival Proteins J. Biol. Chem., October 7, 2005; 280(40): 34233 - 34244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Furuya, T. Kiyota, S. Lee, T. Inoue, G. Sugihara, A. Logvinova, P. Goldsmith, and H. M. Ellerby Nanotubules Formed by Highly Hydrophobic Amphiphilic {alpha}-Helical Peptides and Natural Phospholipids Biophys. J., March 1, 2003; 84(3): 1950 - 1959. [Abstract] [Full Text] [PDF]
|
|
