Abstract
Leishmaniasis, caused by Leishmania parasites, is an important public health problem worldwide. Leishmania, like other trypanosomatids, present unique biological features as compared to higher eukaryotes that can be exploited with the intent of finding new chemotherapeutical/vaccine candidates. Mechanisms of cellular sorting in Leishmania can be viewed as such potential targets. We have previously demonstrated a role for the pro-domain of a Leishmania cysteine proteinase in lysosomal targeting. In this paper, we show that this signal is not recognized by mammalian cells and is recognized by yeast; we also discuss here the implications of these findings related to evolution and further characterization of the Leishmania trafficking machinery.
This is a preview of subscription content, log in via an institution to check access.
References
Al-Qahtani A, Teilhet M, Mensa-Wilmot K (1998) Species-specificity in endoplasmic reticulum signal peptide utilization revealed by proteins from Trypanosoma brucei and Leishmania. Biochem J 331:521–529
Bonangelino CJ, Chavez EM, Bonifacino JS (2002) Genomic screen for vacuolar protein sorting genes in Saccharomyces cerevisiae. Mol Biol Cell 13:2486–2501
Boukai LK, Costa-Pinto D, Soares MJ, McMahon-Pratt D, Traub-Cseko YM (2000) Trafficking of cysteine proteinases to Leishmania lysosomes: lack of involvement of glycosylation. Mol Biochem Parasitol 107:321–325
Cazzulo JJ, Hellman U, Couso R, Parodi AJ (1990) Amino acid and carbohydrate composition of a lysosomal cysteine proteinase from Trypanosoma cruzi. Absence of phosphorylated mannose residues. Mol Biochem Parasitol 38:41–48
Costa-Pinto D, Trinidade LS, McMahon-Pratt D, Traub-Cseko YM (2001) Cellular trafficking in trypanosomatids: a new target for therapies. Int J Parasitol 31:537–544
Gal S, Raikhel NV (1994) A carboxy-terminal plant vacuolar targeting signal is not recognized by yeast. Plant J 6:235–240
Huete-Perez JA, Engel JC, Brinen LS, Mottram JC, McKerrow JH (1999) Protease trafficking in two primitive eukaryotes is mediated by a prodomain protein motif. J Biol Chem 274:16249–16256
Kucharczyk R, Rytka J (2001) Saccharomyces cerevisiae—a model organism for the studies on vacuolar transport. Acta Biochim Pol 48:1025–1042
Li J, Xu H, Bentley WE, Rao G (2002) Impediments to secretion o green fluorescent protein and its fusion from Saccharomyces cerevisiae. Biotechnol Prog 18:831–838
Martinez E, Seguí-Real B, Silles E, Mazón MJ, Sandoval IV (1999) The propeptide of vacuolar aminopeptidase I is necessary and sufficient to target the fluorescent protein GFP to the vacuole of yeast by the Cvt pathway. Mol Microbiol 33:52–62
McConville MJ, Mullin KA, Ilgoutz SC, Teasdale RD (2002) Secretory pathway of trypanosomatid parasites. Microbiol Mol Biol Rev 66:122–154
McIntyre GF, Erickson AH (1991) Procathepsins L and D are membrane bound in acidic microsomal vesicles. J Biol Chem 266:15438–15445
McIntyre GF, Godbold GD, Erickson AH (1994) The pH-dependent membrane association of procathepsin L is mediated by a 9-residue sequence within the propeptide. J Biol Chem 269:567–572
Mottram JC, North MJ, Barry JD, Coombs GH (1989) A cysteine proteinase cDNA from Trypanosoma brucei predicts an enzyme with an unusual C-terminal. FEBS Lett 258:211–215
Nielsen MS, Madsen P, Christensen EI, Nykjaer A, Gliemann J, Kasper D, Pohlmann R, Petersen CM (2001) The sortilin cytoplasmic tail conveys Golgi endosome transport and binds the VHS domain of the GGA2 sorting protein. EMBO J 20:2180–2190
Nishimura Y, Kato K (1992) Expression of mouse cathepsin L cDNA in Saccharomyces cerevisae: evidence that cathepsin L is sorted for targeting to yeast vacuole. Arch Biochem Biophys 298:318–324
Oda MN, Scott SV, Hefner-Gravink A, Caffarelli AD, Klionsky DJ (1996) Identification of a cytoplasm to vacuole targeting determinant in aminopeptidase I. J Cell Biol 132:999–1010
Ramirez MI, Boscardin SB, Han SW, Paranhos-Baccala G, Yoshida N, Kelly JM, Mortara RA, Da Silveira JF (1999) Heterologous expression of a Trypanosoma cruzi surface glycoprotein (gp82) in mammalian cells indicates the existence of different signal sequence requirements and processing. J Eukaryot Microbiol 46:557–565
Reggiori F, Klionsky DJ (2002) Autophagy in the eukaryotic cell. Eukaryot Cell 1:11–21
Roitsch T, Lehle L (1991) The vacuolar protein-targeting signal of yeast carboxypeptidase is functional in oocytes from Xenopus laevis. Eur J Biochem 195:145–150
Sajid M, McKerrow JH (2002) Cysteine proteases of parasitic organisms. Mol Biochem Parasitol 120:1–21
Traub-Cseko YM, Duboise M, Boukai LK, McMahon-Pratt D (1993) Identification of two distinct cysteine proteinase genes of Leishmania pifanoi axenic amastigotes using the polymerase chain reaction. Mol Biochem Parasitol 57:101–116
Wiedmann M, Huth A, Rapoport TA (1984) Xenopus oocytes can secrete bacterial beta-lactamase. Nature 309:637–639
Aknowledgments
We are thankful to Dr. Diane McMahon-Pratt and Dr. Norma Andrews from Yale University and Dr. Peter W. Mason from the University of Texas Medical Branch for initial experiments on the recognition of the Leishmania lysosomal targeting signal in mammalian cells, and to Dr. Juliana M. F. Dutra for help with the figures. This work was supported by PAPES IV-Fiocruz, CNPq, and Instituto Oswaldo Cruz-Fiocruz. Marcel Marín received fellowships from COLCIENCIAS and Instituto Oswaldo Cruz-FIOCRUZ.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Marín-Villa, M., Sampaio Morgado, G., Roy, D. et al. Leishmania lysosomal targeting signal is recognized by yeast and not by mammalian cells. Parasitol Res 103, 983–988 (2008). https://doi.org/10.1007/s00436-008-1047-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00436-008-1047-8