Characterization of Glycosomal RING Finger Proteins of Trypanosomatids

Overview

Journal Exp Parasitol

Specialty Parasitology

Date 2006 Dec 26

PMID 17188680

Citations 3

Authors

Tracy Saveria

Peter Kessler

Bryan C Jensen

Marilyn Parsons

Affiliations

Soon will be listed here.

Abstract

The glycosomes of trypanosomatids are essential organelles that are evolutionarily related to peroxisomes of other eukaryotes. The peroxisomal RING proteins-PEX2, PEX10 and PEX12-comprise a network of integral membrane proteins that function in the matrix protein import cycle. Here, we describe PEX10 and PEX12 in Trypanosoma brucei, Leishmania major, and Trypanosoma cruzi. We expressed GFP fusions of each T. brucei coding region in procyclic form T. brucei, where they localized to glycosomes and behaved as integral membrane proteins. Despite the weak transmembrane predictions for TbPEX12, protease protection assays demonstrated that both the N and C termini are cytosolic, similar to mammalian PEX12. 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.

Citing Articles

Glycosome heterogeneity in kinetoplastids.

Crowe L, Morris M Biochem Soc Trans. 2021; 49(1):29-39.

PMID: 33439256 PMC: 7925000. DOI: 10.1042/BST20190517.

Environmentally regulated glycosome protein composition in the African trypanosome.

Bauer S, Morris J, Morris M Eukaryot Cell. 2013; 12(8):1072-9.

PMID: 23709182 PMC: 3754536. DOI: 10.1128/EC.00086-13.

Conservation of PEX19-binding motifs required for protein targeting to mammalian peroxisomal and trypanosome glycosomal membranes.

Saveria T, Halbach A, Erdmann R, Volkmer-Engert R, Landgraf C, Rottensteiner H Eukaryot Cell. 2007; 6(8):1439-49.

PMID: 17586720 PMC: 1951143. DOI: 10.1128/EC.00084-07.

References

Wirtz E, Leal S, Ochatt C, Cross G . A tightly regulated inducible expression system for conditional gene knock-outs and dominant-negative genetics in Trypanosoma brucei. Mol Biochem Parasitol. 1999; 99(1):89-101. DOI: 10.1016/s0166-6851(99)00002-x. View

Anderson S, Carter V, Hagen C, Parsons M . Molecular cloning of the glycosomal malate dehydrogenase of Trypanosoma brucei. Mol Biochem Parasitol. 1998; 96(1-2):185-9. DOI: 10.1016/s0166-6851(98)00116-9. View

Hill K, Hutchings N, Russell D, Donelson J . A novel protein targeting domain directs proteins to the anterior cytoplasmic face of the flagellar pocket in African trypanosomes. J Cell Sci. 1999; 112 Pt 18:3091-101. DOI: 10.1242/jcs.112.18.3091. View

Platta H, Girzalsky W, Erdmann R . Ubiquitination of the peroxisomal import receptor Pex5p. Biochem J. 2004; 384(Pt 1):37-45. PMC: 1134086. DOI: 10.1042/BJ20040572. View

Jensen B, Brekken D, Randall A, Kifer C, Parsons M . Species specificity in ribosome biogenesis: a nonconserved phosphoprotein is required for formation of the large ribosomal subunit in Trypanosoma brucei. Eukaryot Cell. 2005; 4(1):30-5. PMC: 544161. DOI: 10.1128/EC.4.1.30-35.2005. View

Kiel J, Emmrich K, Meyer H, Kunau W . Ubiquitination of the peroxisomal targeting signal type 1 receptor, Pex5p, suggests the presence of a quality control mechanism during peroxisomal matrix protein import. J Biol Chem. 2004; 280(3):1921-30. DOI: 10.1074/jbc.M403632200. View

Kragt A, Voorn-Brouwer T, van den Berg M, Distel B . The Saccharomyces cerevisiae peroxisomal import receptor Pex5p is monoubiquitinated in wild type cells. J Biol Chem. 2005; 280(9):7867-74. DOI: 10.1074/jbc.M413553200. View

Kessler P, Parsons M . Probing the role of compartmentation of glycolysis in procyclic form Trypanosoma brucei: RNA interference studies of PEX14, hexokinase, and phosphofructokinase. J Biol Chem. 2005; 280(10):9030-6. DOI: 10.1074/jbc.M412033200. View

Banerjee S, Kessler P, Saveria T, Parsons M . Identification of trypanosomatid PEX19: functional characterization reveals impact on cell growth and glycosome size and number. Mol Biochem Parasitol. 2005; 142(1):47-55. DOI: 10.1016/j.molbiopara.2005.03.008. View

10.

El-Sayed N, Myler P, Blandin G, Berriman M, Crabtree J, Aggarwal G . Comparative genomics of trypanosomatid parasitic protozoa. Science. 2005; 309(5733):404-9. DOI: 10.1126/science.1112181. View

11.

El-Sayed N, Myler P, Bartholomeu D, Nilsson D, Aggarwal G, Tran A . The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease. Science. 2005; 309(5733):409-15. DOI: 10.1126/science.1112631. View

12.

Berriman M, Ghedin E, Hertz-Fowler C, Blandin G, Renauld H, Bartholomeu D . The genome of the African trypanosome Trypanosoma brucei. Science. 2005; 309(5733):416-22. DOI: 10.1126/science.1112642. View

13.

Ivens A, Peacock C, Worthey E, Murphy L, Aggarwal G, Berriman M . The genome of the kinetoplastid parasite, Leishmania major. Science. 2005; 309(5733):436-42. PMC: 1470643. DOI: 10.1126/science.1112680. View

14.

Platta H, Grunau S, Rosenkranz K, Girzalsky W, Erdmann R . Functional role of the AAA peroxins in dislocation of the cycling PTS1 receptor back to the cytosol. Nat Cell Biol. 2005; 7(8):817-22. DOI: 10.1038/ncb1281. View

15.

Kiel J, Otzen M, Veenhuis M, van der Klei I . Obstruction of polyubiquitination affects PTS1 peroxisomal matrix protein import. Biochim Biophys Acta. 2005; 1745(2):176-86. DOI: 10.1016/j.bbamcr.2005.01.004. View

16.

Krazy H, Michels P . Identification and characterization of three peroxins--PEX6, PEX10 and PEX12--involved in glycosome biogenesis in Trypanosoma brucei. Biochim Biophys Acta. 2006; 1763(1):6-17. DOI: 10.1016/j.bbamcr.2005.11.002. View

17.

Claypool S, McCaffery J, Koehler C . Mitochondrial mislocalization and altered assembly of a cluster of Barth syndrome mutant tafazzins. J Cell Biol. 2006; 174(3):379-90. PMC: 2064234. DOI: 10.1083/jcb.200605043. View

18.

Chang C, Warren D, Sacksteder K, Gould S . PEX12 interacts with PEX5 and PEX10 and acts downstream of receptor docking in peroxisomal matrix protein import. J Cell Biol. 1999; 147(4):761-74. PMC: 2156163. DOI: 10.1083/jcb.147.4.761. View

19.

Okumoto K, Abe I, Fujiki Y . Molecular anatomy of the peroxin Pex12p: ring finger domain is essential for Pex12p function and interacts with the peroxisome-targeting signal type 1-receptor Pex5p and a ring peroxin, Pex10p. J Biol Chem. 2000; 275(33):25700-10. DOI: 10.1074/jbc.M003303200. View

20.

Joazeiro C, Weissman A . RING finger proteins: mediators of ubiquitin ligase activity. Cell. 2000; 102(5):549-52. DOI: 10.1016/s0092-8674(00)00077-5. View