This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Triggs, V. P.
Right arrow Articles by Bangs, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Triggs, V. P.
Right arrow Articles by Bangs, J. D.

 Previous Article  |  Next Article 

Eukaryotic Cell, February 2003, p. 76-83, Vol. 2, No. 1
1535-9778/03/$08.00+0     DOI: 10.1128/EC.2.1.76-83.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Glycosylphosphatidylinositol-Dependent Protein Trafficking in Bloodstream Stage Trypanosoma brucei

Veronica P. Triggs1 and James D. Bangs2*

Department of Biomolecular Chemistry,1 Department of Medical Microbiology and Immunology, University of Wisconsin-Madison Medical School, Madison, Wisconsin 537062

Received 13 September 2002/ Accepted 4 November 2002

We have previously demonstrated that glycosylphosphatidylinositol (GPI) anchors strongly influence protein trafficking in the procyclic insect stage of Trypanosoma brucei (M. A. McDowell, D. A. Ransom, and J. D. Bangs, Biochem. J. 335:681-689, 1998), where GPI-minus variant surface glycoprotein (VSG) reporters have greatly reduced rates of endoplasmic reticulum (ER) exit but are ultimately secreted. We now demonstrate that GPI-dependent trafficking also occurs in pathogenic bloodstream trypanosomes. However, unlike in procyclic trypanosomes, truncated VSGs lacking C-terminal GPI-addition signals are not secreted but are mistargeted to the lysosome and degraded. Failure to export these reporters is not due to a deficiency in secretion of these cells since the N-terminal ATPase domain of the endogenous ER protein BiP is efficiently secreted from transgenic cell lines. Velocity sedimentation experiments indicate that GPI-minus VSG dimerizes similarly to wild-type VSG, suggesting that degradation is not due to ER quality control mechanisms. However, GPI-minus VSGs are fully protected from degradation by the cysteine protease inhibitor FMK024, a potent inhibitor of the major lysosomal protease trypanopain. Immunofluorescence of cells incubated with FMK024 demonstrates that GPI-minus VSG colocalizes with p67, a lysosomal marker. These data suggest that in the absence of a GPI anchor, VSG is mistargeted to the lysosome and subsequently degraded. Our findings indicate that GPI-dependent transport is a general feature of secretory trafficking in both stages of the life cycle. A working model is proposed in which GPI valence regulates progression in the secretory pathway of bloodstream stage trypanosomes.

* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison Medical School, Madison, WI 53706. Phone: (608) 262-3110. Fax: (608) 262-8418. E-mail: jdbangs{at}facstaff.wisc.edu.

Eukaryotic Cell, February 2003, p. 76-83, Vol. 2, No. 1
1535-9778/03/$08.00+0     DOI: 10.1128/EC.2.1.76-83.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Goldshmidt, H., Sheiner, L., Butikofer, P., Roditi, I., Uliel, S., Gunzel, M., Engstler, M., Michaeli, S. (2008). Role of Protein Translocation Pathways across the Endoplasmic Reticulum in Trypanosoma brucei. J. Biol. Chem. 283: 32085-32098 [Abstract] [Full Text]  
  • O'Brien, T. C., Mackey, Z. B., Fetter, R. D., Choe, Y., O'Donoghue, A. J., Zhou, M., Craik, C. S., Caffrey, C. R., McKerrow, J. H. (2008). A Parasite Cysteine Protease Is Key to Host Protein Degradation and Iron Acquisition. J. Biol. Chem. 283: 28934-28943 [Abstract] [Full Text]  
  • Sutterwala, S. S., Creswell, C. H., Sanyal, S., Menon, A. K., Bangs, J. D. (2007). De Novo Sphingolipid Synthesis Is Essential for Viability, but Not for Transport of Glycosylphosphatidylinositol-Anchored Proteins, in African Trypanosomes. Eukaryot Cell 6: 454-464 [Abstract] [Full Text]  
  • Schwartz, K. J., Peck, R. F., Tazeh, N. N., Bangs, J. D. (2005). GPI valence and the fate of secretory membrane proteins in African trypanosomes. J. Cell Sci. 118: 5499-5511 [Abstract] [Full Text]  
  • Engstler, M., Weise, F., Bopp, K., Grunfelder, C. G., Gunzel, M., Heddergott, N., Overath, P. (2005). The membrane-bound histidine acid phosphatase TbMBAP1 is essential for endocytosis and membrane recycling in Trypanosoma brucei. J. Cell Sci. 118: 2105-2118 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»