Isolation and characterization of Leishmania mutants defective in glycosomal protein import

Mannion-Henderson, Jane; Flaspohler, John A.; Lemley, Kayde; Rickoll, Wayne L.; Parsons, Marilyn

doi:10.1016/s0166-6851(99)00215-7

Cited by 9 publications

(3 citation statements)

References 35 publications

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“…We have called this protein GIM5; here, GIM stands for glycosome integral membrane protein. (The preceding numbers, GIM1–4, identify genes in Leishmania strains that show defects in glycosomal matrix protein import; Mannion‐Henderson et al ., 2000.) Antibodies directed against two peptides derived from the GIM5 sequence detected a 26 kDa protein present at similar levels in both bloodstream and procyclic (tset‐tse fly form) trypanosomes, and Northern blot hybridization revealed the existence of two constitutively expressed mRNAs of 1.8 kb and 1.35 kb (not shown).…”

Section: Resultsmentioning

confidence: 99%

An essential dimeric membrane protein of trypanosome glycosomes

Maier¹,

Lorenz²,

Voncken

et al. 2001

Molecular Microbiology

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Kinetoplastid parasites compartmentalize the first seven enzymes of glycolysis in a peroxisome‐like microbody, the glycosome. Genes encoding the most abundant protein of the glycosomal membrane, GIM5, have been cloned and the protein characterized. Two genes, GIM5A and GIM5B, encode 26 kDa proteins. Although many microbody membrane proteins are conserved in evolution, the only homologues of GIM5 in the available databases are from the closely related kinetoplastids Trypanosoma cruzi and Leishmania. The N‐ and C‐termini are conserved between the two genes, and between species, and are oriented towards the cytosol. They are separated by a short loop that is located between two transmembrane domains and shows almost no sequence conservation. This suggests that the N‐ and C‐terminal domains are more important for function. GIM5 forms dimers in vivo. Overexpression of GIM5B inhibits growth, whereas depletion of GIM5 to below 10% of wild‐type levels is very rapidly lethal. This novel organellar membrane protein is therefore essential for bloodstream trypanosome survival.

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Section: Resultsmentioning

confidence: 99%

An essential dimeric membrane protein of trypanosome glycosomes

Maier¹,

Lorenz²,

Voncken

et al. 2001

Molecular Microbiology

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show abstract

“…Other glycosomal enzymes, GAPDH and PGK-C (having a PTS1 and an unknown targeting signal, respectively), remained correctly compartmentalized and glycosome morphology and number were not significantly affected [279]. The same methodology has subsequently yielded two additional mutant clones (called gim2 and gim4) that have partial defects in glycosomal import of HGPRT and TIM, but not GAPDH and PGK-C, but no obvious glycosomal or other structural changes compared to wildtype cells [281]. The gim1-1 mutant gene was identified as a PEX2 homologue.…”

Section: Peroxins Involved In Glycosome Biogenesismentioning

confidence: 97%

“…The phenotype was due to the dominant-negative nonsense mutation in one of the two PEX2 alleles of the diploid organism [280], resulting in a protein lacking one transmembrane domain and the RING finger. The same methodology has subsequently yielded two additional mutant clones (called gim2 and gim4) that have partial defects in glycosomal import of HGPRT and TIM, but not GAPDH and PGK-C, but no obvious glycosomal or other structural changes compared to wildtype cells [281]. The gim2 and gim4 genes remain to be characterized.…”

Section: Peroxins Involved In Glycosome Biogenesismentioning

confidence: 99%

Biogenesis of peroxisomes and glycosomes: trypanosomatid glycosome assembly is a promising new drug target

et al. 2004

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In trypanosomatids (Trypanosoma and Leishmania), protozoa responsible for serious diseases of mankind in tropical and subtropical countries, core carbohydrate metabolism including glycolysis is compartmentalized in peculiar peroxisomes called glycosomes. Proper biogenesis of these organelles and the correct sequestering of glycolytic enzymes are essential to these parasites. Biogenesis of glycosomes in trypanosomatids and that of peroxisomes in other eukaryotes, including the human host, occur via homologous processes involving proteins called peroxins, which exert their function through multiple, transient interactions with each other. Decreased expression of peroxins leads to death of trypanosomes. Peroxins show only a low level of sequence conservation. Therefore, it seems feasible to design compounds that will prevent interactions of proteins involved in biogenesis of trypanosomatid glycosomes without interfering with peroxisome formation in the human host cells. Such compounds would be suitable as lead drugs against trypanosomatid-borne diseases.

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Treatment Modalities for Cutaneous and Visceral Leishmaniasis

McGwire

2014

Pathogenesis of Leishmaniasis

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Isolation and characterization of Leishmania mutants defective in glycosomal protein import

Cited by 9 publications

References 35 publications

An essential dimeric membrane protein of trypanosome glycosomes

An essential dimeric membrane protein of trypanosome glycosomes

Biogenesis of peroxisomes and glycosomes: trypanosomatid glycosome assembly is a promising new drug target

Treatment Modalities for Cutaneous and Visceral Leishmaniasis

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