MOLECULAR ANALYSIS OF THE GLYCOSOME.

Summary

Principal Investigator: Marilyn Parsons
Abstract: DESCRIPTION (Adapted from the Applicant's Abstract): Members of the order kinetoplastida are the causative agents of African sleeping sickness (Trypanosoma brucei subspecies), leishmaniasis (Leishmania spp.) and Chagas' disease (Trypanosoma cruzi). There is no vaccine against any of these diseases and current treatments are toxic. The parasite possesses a unique subcellular organelle, the clycosome, which is a distant relative of the peroxisome found in higher eukaryotes. The glycosome houses many of the enzymes of the Embden-Meyerhof pathway of glycolysis, as well as enzymes involved in nucleotide biosynthesis, ether-lipid biosynthesis, Beta-oxidation of fatty acids, purine salvage and pyrimidine biosynthesis. Given the importance of these metabolic pathways to the parasite, the glycosome and its constitution's have been recognized as a possible target for the development of new chemotherapies. Their studies are aimed at understanding glycosomal biogenesis and protein input and the relationship of these processes and the molecules involved to peroxisome biogenesis in the human host.
Funding Period: 1986-12-01 - 2006-05-31
more information: NIH RePORT

Top Publications

  1. pmc Compartmentation prevents a lethal turbo-explosion of glycolysis in trypanosomes
    Jurgen R Haanstra
    Department of Molecular Cell Physiology, Faculty of Earth and Life Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1085, NL 1081 HV, Amsterdam, The Netherlands
    Proc Natl Acad Sci U S A 105:17718-23. 2008
  2. ncbi Probing the role of compartmentation of glycolysis in procyclic form Trypanosoma brucei: RNA interference studies of PEX14, hexokinase, and phosphofructokinase
    Peter S Kessler
    Seattle Biomedical Research Institute, Seattle, Washington 98109, USA
    J Biol Chem 280:9030-6. 2005
  3. ncbi Identification of trypanosomatid PEX19: functional characterization reveals impact on cell growth and glycosome size and number
    Sanjiban K Banerjee
    Seattle Biomedical Research Institute, 307 Westlake Avenue N, Seattle, WA 98109, USA
    Mol Biochem Parasitol 142:47-55. 2005
  4. pmc Characterization of glycosomal RING finger proteins of trypanosomatids
    Tracy Saveria
    Seattle Biomedical Research Institute, 307 Westlake Avenue N, Seattle, WA 98109, USA
    Exp Parasitol 116:14-24. 2007
  5. pmc Conservation of PEX19-binding motifs required for protein targeting to mammalian peroxisomal and trypanosome glycosomal membranes
    Tracy Saveria
    Seattle Biomedical Research Institute, Seattle, WA 98109, USA
    Eukaryot Cell 6:1439-49. 2007

Detail Information

Publications5

  1. pmc Compartmentation prevents a lethal turbo-explosion of glycolysis in trypanosomes
    Jurgen R Haanstra
    Department of Molecular Cell Physiology, Faculty of Earth and Life Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1085, NL 1081 HV, Amsterdam, The Netherlands
    Proc Natl Acad Sci U S A 105:17718-23. 2008
    ..This provides the first experimental support for our hypothesis that pathway compartmentation is an alternative to allosteric regulation...
  2. ncbi Probing the role of compartmentation of glycolysis in procyclic form Trypanosoma brucei: RNA interference studies of PEX14, hexokinase, and phosphofructokinase
    Peter S Kessler
    Seattle Biomedical Research Institute, Seattle, Washington 98109, USA
    J Biol Chem 280:9030-6. 2005
    ..Taken together, these data indicate that the glycosome provides significant, but not complete, protection of trypanosomes from the dangerous design of glycolysis...
  3. ncbi Identification of trypanosomatid PEX19: functional characterization reveals impact on cell growth and glycosome size and number
    Sanjiban K Banerjee
    Seattle Biomedical Research Institute, 307 Westlake Avenue N, Seattle, WA 98109, USA
    Mol Biochem Parasitol 142:47-55. 2005
    ..Surprisingly, a four-fold increase in the size of the remaining glycosomes was observed. We propose that this phenotype of fewer but larger glycosomes results from the reduction in import of glycosomal membrane proteins...
  4. pmc Characterization of glycosomal RING finger proteins of trypanosomatids
    Tracy Saveria
    Seattle Biomedical Research Institute, 307 Westlake Avenue N, Seattle, WA 98109, USA
    Exp Parasitol 116:14-24. 2007
    ..GFP fusions of T. cruzi PEX10 and L. major PEX12 also localized to glycosomes in T. brucei indicating that glycosomal membrane protein targeting is conserved across trypanosomatids...
  5. pmc Conservation of PEX19-binding motifs required for protein targeting to mammalian peroxisomal and trypanosome glycosomal membranes
    Tracy Saveria
    Seattle Biomedical Research Institute, Seattle, WA 98109, USA
    Eukaryot Cell 6:1439-49. 2007
    ..However, in contrast to T. brucei PEX10 and PEX12, T. brucei PEX14 does not traffic to human peroxisomes, indicating that it is not recognized by the human PEX14 import mechanism...