Volume 272, Number 19, Issue of May 9, 1997 pp. 12482-12491
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Proteins with Glycosylphosphatidylinositol (GPI) Signal Sequences Have Divergent Fates during a GPI Deficiency
GPIs ARE ESSENTIAL FOR NUCLEAR DIVISION IN TRYPANOSOMA CRUZI

(Received for publication, January 16, 1997, and in revised form, March 6, 1997)

From the Department of Cellular Biology, The University of Georgia, Athens, Georgia 30602

Glycosylphosphatidylinositols (GPIs) are membrane anchors for cell surface proteins of several major protozoan parasites of humans, including Trypanosoma cruzi, the causative agent of Chagas' disease. To investigate the general role of GPIs in T. cruzi, we generated GPI-deficient parasites by heterologous expression of T. brucei GPI-phospholipase C. Putative protein-GPI intermediates were depleted, causing the biochemical equivalent of a dominant-negative loss of function mutation in the GPI pathway. Cell surface expression of major GPI-anchored proteins was diminished in GPI-deficient T. cruzi. Four proteins that are normally GPI-anchored in T. cruzi exhibited different fates during the GPI shortage; Ssp-4 and p75 were secreted prematurely, while protease gp50/55 and p60 were degraded intracellularly. These observations demonstrate that secretion and intracellular degradation of GPI-anchored proteins may occur in the same genetic background during a GPI deficiency. We postulate that the interaction between a protein-GPI transamidase and the COOH-terminal GPI signal sequence plays a pivotal role in determining the fate of these proteins.

At a nonpermissive GPI deficiency, T. cruzi amastigotes inside mammalian cells replicated their single kinetoplast but failed at mitosis. Hence, in these protozoans, GPIs appear to be essential for nuclear division, but not for mitochondrial duplication.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				V. Bhatia, M. Sinha, B. Luxon, and N. Garg Utility of the Trypanosoma cruzi Sequence Database for Identification of Potential Vaccine Candidates by In Silico and In Vitro Screening Infect. Immun., November 1, 2004; 72(11): 6245 - 6254. [Abstract] [Full Text] [PDF]

				Z. Zheng, K. D. Butler, R. K. Tweten, and K. Mensa-Wilmot Endosomes, Glycosomes, and Glycosylphosphatidylinositol Catabolism in Leishmania major J. Biol. Chem., October 1, 2004; 279(40): 42106 - 42113. [Abstract] [Full Text] [PDF]

				E. Lalanne, D. Honys, A. Johnson, G. H. H. Borner, K. S. Lilley, P. Dupree, U. Grossniklaus, and D. Twell SETH1 and SETH2, Two Components of the Glycosylphosphatidylinositol Anchor Biosynthetic Pathway, Are Required for Pollen Germination and Tube Growth in Arabidopsis PLANT CELL, January 1, 2004; 16(1): 229 - 240. [Abstract] [Full Text] [PDF]

				S. Lillico, M. C. Field, P. Blundell, G. H. Coombs, and J. C. Mottram Essential Roles for GPI-anchored Proteins in African Trypanosomes Revealed Using Mutants Deficient in GPI8 Mol. Biol. Cell, March 1, 2003; 14(3): 1182 - 1194. [Abstract] [Full Text] [PDF]

				B. S. McGwire, W. A. O'Connell, K.-P. Chang, and D. M. Engman Extracellular Release of the Glycosylphosphatidylinositol (GPI)-linked Leishmania Surface Metalloprotease, gp63, Is Independent of GPI Phospholipolysis. IMPLICATIONS FOR PARASITE VIRULENCE J. Biol. Chem., March 8, 2002; 277(11): 8802 - 8809. [Abstract] [Full Text] [PDF]

				M. J. McConville, K. A. Mullin, S. C. Ilgoutz, and R. D. Teasdale Secretory Pathway of Trypanosomatid Parasites Microbiol. Mol. Biol. Rev., March 1, 2002; 66(1): 122 - 154. [Abstract] [Full Text] [PDF]

				I. C. Almeida and R. T. Gazzinelli Proinflammatory activity of glycosylphosphatidylinositol anchors derived from Trypanosoma cruzi: structural and functional analyses J. Leukoc. Biol., October 1, 2001; 70(4): 467 - 477. [Abstract] [Full Text] [PDF]

				A. C. S. Monteiro, M. Abrahamson, A. P. C. A. Lima, M. A. Vannier-Santos, and J. Scharfstein Identification, characterization and localization of chagasin, a tight-binding cysteine protease inhibitor in Trypanosoma cruzi J. Cell Sci., January 11, 2001; 114(21): 3933 - 3942. [Abstract] [Full Text] [PDF]

				D. A. Armah and K. Mensa-Wilmot S-Myristoylation of a Glycosylphosphatidylinositol-specific Phospholipase C in Trypanosoma brucei J. Biol. Chem., February 26, 1999; 274(9): 5931 - 5938. [Abstract] [Full Text] [PDF]

				M. Cardoso De Almeida, M Geuskens, and E Pays Cell lysis induces redistribution of the GPI-anchored variant surface glycoprotein on both faces of the plasma membrane of Trypanosoma brucei J. Cell Sci., January 12, 1999; 112(23): 4461 - 4473. [Abstract] [PDF]

				H. P. Low, M. A. M. Santos, B. Wizel, and R. L. Tarleton Amastigote Surface Proteins of Trypanosoma cruzi Are Targets for CD8+ CTL J. Immunol., February 15, 1998; 160(4): 1817 - 1823. [Abstract] [Full Text] [PDF]

				D. A. Armah and K. Mensa-Wilmot Tetramerization of Glycosylphosphatidylinositol-specific Phospholipase C from Trypanosoma brucei J. Biol. Chem., June 16, 2000; 275(25): 19334 - 19342. [Abstract] [Full Text] [PDF]