The Leishmania promastigote surface antigen 2 complex is differentially expressed during the parasite life cycle

Handman, Emanuela; Osborn, Amelia H.; Symons, F. M.; Driel, Roel van; Cappai, Roberto

doi:10.1016/0166-6851(95)02500-6

Cited by 49 publications

(32 citation statements)

References 29 publications

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“…A number of amastigote-specific genes have been identified, including a 3′-nucleotidase [7], the A2 gene family [8,9], HSP100 [10], and a MAP kinase, LMPMK [11]. In addition, certain members of the GP63 and PSA-2 gene families are differentially expressed in amastigotes, and there are differences in the GPI anchor of the latter [12]. In contrast, some processes are down-regulated in amastigotes [13,14], most notably lipophosphglycan (LPG) biosynthesis, resulting in its replacement by glycoinositol phosholipid (GIPL) as the major component of the parasite surface coat [13].…”

Section: Introductionmentioning

confidence: 99%

Analysis of the Leishmania donovani transcriptome reveals an ordered progression of transient and permanent changes in gene expression during differentiation

Saxena

Lahav

Holland

et al. 2007

Molecular and Biochemical Parasitology

148

140

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Leishmania donovani is an intracellular protozoan parasite that causes kala-azar in humans. During infection the extracellular insect forms (promastigotes) undergo rapid differentiation to intracellular amastigotes that proliferates in phagolysosomes of mammalian macrophages. We used microarraybased expression profiling to investigate the time-course of changes in RNA abundance during promastigote-to-amastigote differentiation in a host-free system that mimics this process. These studies revealed that several hundred genes underwent an ordered progression of transient or permanent up-and down-regulation during differentiation. Genes that were permanently upregulated in amastigotes were enriched for transporters and surface proteins, but under-represented in genes involved in protein and other metabolism. Most of these changes occurred late in the differentiation process, when morphological differentiation was essentially complete. Downregulated genes were over-represented in those involved in cell motility, growth and/or maintenance, and these changes generally occurred earlier in the process. Genes that were transiently up-or downregulated during differentiation included those encoding heat shock proteins, ubiquitin hydrolases, RNA binding proteins, protein kinases, a protein phosphatase, and a histone deacetylase. These results suggest that changes in mRNA abundance may be important in signal transduction, as well as protein and mRNA turnover, during differentiation. In addition to these mRNA changes, other transcripts including one or more rRNAs and snoRNAs, and non-coding RNAs from several telomeres, also showed substantial changes in abundance during the differentiation process. This paper provides the first genome-scale quantitative analysis of gene expression during the transition from promastigotes to amastigotes and demonstrates the utility of the host-free differentiation system.

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Section: Introductionmentioning

confidence: 99%

Analysis of the Leishmania donovani transcriptome reveals an ordered progression of transient and permanent changes in gene expression during differentiation

Saxena

Lahav

Holland

et al. 2007

Molecular and Biochemical Parasitology

148

140

View full text Add to dashboard Cite

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“…[8][9][10][11] Although this major transformation's molecular basis remains poorly understood, several studies have shown that developmentally expressed transcript post-transcription regulation involves sequences present mainly in the 3Ј-untranslated regions. [12][13][14] Post-transcription control predominance over transcription control is probably due to trypanosomatid genome organization in large polycistronic transcription units. Several amastigote-specific genes have been described in different Leishmania species, including hsp83, hsp100, histone H1, cpb cysteine proteinase, the A2 gene family, the LmcDNA16 gene family, the spliced leader RNA gene, and the Ca 2ϩ -ATPase gene.…”

Section: Introductionmentioning

confidence: 99%

Cultivation and characterization of stable Leishmania guyanensis complex axenic amastigotes derived from infected U937 cells.

Puentes¹,

Díaz²,

Hoya³

et al. 2000

The American Journal of Tropical Medicine and Hygiene

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Abstract. The study of the differential regulation of several genes, in both Leishmania parasite life cycle forms, has been simplified by the development of in vitro axenic amastigote culture. Different reports have described extracellular amastigote production and maintenance from several Leishmania spp. A general approach to induce amastigote-like transformation includes progressive pH and temperature changes. Production of axenic amastigotes in continuous cultures using amastigotes recovered from macrophages is described in this report. Leishmania (Viannia) panamensis (M/HOM/PA/71/LS94) and Leishmania (V). guyanensis (M/HOM/BR/75/M4147) intracellular amastigotes were recovered from the human macrophage-like U937 cell line previously infected with promastigotes. The parasites were immediately adapted for growth and kept as axenic amastigotes at 34ЊC and acidic pH. These organisms were able to infect macrophage cell lines, maintain amastigote morphologic features, and express stage-specific transcripts. The relevance of axenic amastigotes in characterizing virulence factors in American leishmaniasis is discussed.

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“…However, the fact that these proteins are encoded by multicopy polymorphic genes (Button et al, 1989;Lohman et al, 1990;Symons et al, 1994) has hindered elucidation of their function by genetic analysis (Joshi et al, 1998). Moreover, surface expression of gp63 and PSA2 is dramatically down-regulated in the amastigote stage of some Leishmania species and variable within particular parasite populations of others (Bahr et al, 1993;Handman et al, 1995) such that the precise function of these parasite proteins in the mammalian host remains unclear.Proteins that are destined to receive a GPI anchor are synthesized as precursor proteins with an N-terminal signal sequence that targets the protein to the endoplasmic reticulum (ER) and a C-terminal GPI attachment signal. The latter § Corresponding author.…”

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confidence: 99%

Leishmania mexicanaMutants Lacking Glycosylphosphatidylinositol (GPI):Protein Transamidase Provide Insights into the Biosynthesis and Functions of GPI-anchored Proteins

Hilley

Zawadzki

McConville

et al. 2000

MBoC

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The major surface proteins of the parasitic protozoon Leishmania mexicana are anchored to the plasma membrane by glycosylphosphatidylinositol (GPI) anchors. We have cloned the L. mexicana GPI8 gene that encodes the catalytic component of the GPI:protein transamidase complex that adds GPI anchors to nascent cell surface proteins in the endoplasmic reticulum. Mutants lacking GPI8 (⌬GPI8) do not express detectable levels of GPI-anchored proteins and accumulate two putative protein-anchor precursors. However, the synthesis and cellular levels of other nonprotein-linked GPIs, including lipophosphoglycan and a major class of free GPIs, are not affected in the ⌬GPI8 mutant. Significantly, the ⌬GPI8 mutant displays normal growth in liquid culture, is capable of differentiating into replicating amastigotes within macrophages in vitro, and is infective to mice. These data suggest that GPI-anchored surface proteins are not essential to L. mexicana for its entry into and survival within mammalian host cells in vitro or in vivo and provide further support for the notion that free GPIs are essential for parasite growth. INTRODUCTIONLeishmania are protozoan parasites that cause a spectrum of diseases in humans. These parasites alternate between a flagellated promastigote stage that proliferates within the midgut of the sandfly vector and a nonmotile amastigote stage that invades mammalian macrophages, where they occupy the phagolysosome compartment. The cell surface of the promastigote stage is coated by a protective glycocalyx that comprises a number of glycosylphosphatidylinositol (GPI)-anchored glycoproteins, a complex GPI-anchored lipophosphoglycan (LPG), and a family of free GPIs (termed glycoinositolphospholipids [GIPLs]) Beverley and Turco, 1998; Figure 1). Components in this glycoclayx are thought to be essential for parasite survival and infectivity in the diverse host Beverley and Turco, 1998). The GPIanchored glycoproteins include an abundant metalloproteinase, termed gp63 or leishmanolysin, and the promastigote surface antigen (PSA2)/gp46 family of glycoproteins Murray et al., 1989;Frommel et al., 1990;Lohman et al., 1990). Gp63 has been shown to be proteolytically active against a wide variety of different peptide substrates and has been reported to act as a ligand for macrophage receptors, either directly or after opsonization with complement, to protect the parasites from complementmediated lysis and also to contribute to the pathology of lesion development (see Alexander and Russell, 1992;Joshi et al., 1998). However, the fact that these proteins are encoded by multicopy polymorphic genes (Button et al., 1989;Lohman et al., 1990;Symons et al., 1994) has hindered elucidation of their function by genetic analysis (Joshi et al., 1998). Moreover, surface expression of gp63 and PSA2 is dramatically down-regulated in the amastigote stage of some Leishmania species and variable within particular parasite populations of others (Bahr et al., 1993;Handman et al., 1995) such that the precise function of these parasite pro...

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The Leishmania promastigote surface antigen 2 complex is differentially expressed during the parasite life cycle

Cited by 49 publications

References 29 publications

Analysis of the Leishmania donovani transcriptome reveals an ordered progression of transient and permanent changes in gene expression during differentiation

Analysis of the Leishmania donovani transcriptome reveals an ordered progression of transient and permanent changes in gene expression during differentiation

Cultivation and characterization of stable Leishmania guyanensis complex axenic amastigotes derived from infected U937 cells.

Leishmania mexicanaMutants Lacking Glycosylphosphatidylinositol (GPI):Protein Transamidase Provide Insights into the Biosynthesis and Functions of GPI-anchored Proteins

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