Genes encoding the major surface glycoprotein in Leishmania are tandemly linked at a single chromosomal locus and are constitutively transcribed

Button, Linda L.; Russell, David G.; Klein, Hannah L.; Medina‐Acosta, Enrique; Karess, Roger E.; McMaster, W. Robert

doi:10.1016/0166-6851(89)90076-5

Cited by 124 publications

(46 citation statements)

References 36 publications

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“…A survey of intergenic regions in Leishmania whose poly(A) and splice sites have been mapped reveals spacings from 85 to 660 nucleotides, with an average of 383 and a median of 390 (nine loci; Landfear et al 1986;Lee et al 1988;Kapler et al 1990a;Genske et al 1991;Flinn and Smith 1992). These values are consistent with the spacing inferred from Northern and Southern blot analyses of the HSP83, gp63, and A/D1/D2/B/C loci (Button et al 1989;Shapira and Pinelli 1989;Flinn and Smith 1992;Ramamoorthy et al 1992). Thus, poly(A) sites are always positioned close to downstream splice acceptor sites in Leishmania.…”

Section: Determinants Of Poly(a) Site Selection In Leishmaniasupporting

confidence: 74%

Coupling of poly(A) site selection and trans-splicing in Leishmania.

LeBowitz¹,

Smith²,

Rusché³

et al. 1993

Genes Dev.

327

243

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Intergenic regions of polycistronic pre-mRNAs of trypanosomatid protozoans are the sites of two processing reactions: polyadenylation of the upstream gene and trans-splicing of the capped miniexon to the downstream gene. Their close proximity and the lack of consensus motifs at poly(A) sites led us to test whether poly(A) site selection is governed by the location of the downstream splice acceptor in the DHFR-TS locus of Leishmania major. Whenever the position of the downstream splice site was altered, the poly(A) site was shifted 400-500 nucleotides upstream of the new splice site. In contrast, when the wild-type poly(A) site was eliminated, the downstream splice site was unaffected, and polyadenylation was maintained 200-500 nucleotides upstream of the splice site. In a second set of experiments, T7 RNA polymerase expressed in Leishmania was used to direct the synthesis of artificial pre-RNAs in vivo whose expression was found to require the presence of a downstream splice acceptor. We conclude that poly(A) site selection in Leishmania is specified by the position of the downstream splice acceptor and propose a scanning model for poly(A) site selection after splice site recognition.

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Section: Determinants Of Poly(a) Site Selection In Leishmaniasupporting

confidence: 74%

Coupling of poly(A) site selection and trans-splicing in Leishmania.

LeBowitz¹,

Smith²,

Rusché³

et al. 1993

Genes Dev.

327

243

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“…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 proteins in the mammalian host remains unclear.…”

Section: Introductionmentioning

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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“…All gp63 studied to date in the different Leishmania species share high nucleotide sequence identity and the enzyme has been shown to be encoded by a family of tandemly linked genes, all of which map to a single chromosome [162,163]. Additionally, the crystal structure of gp63 purified from L. major promastigotes reveals that this peptidase is a member of the metzincin family of zinc metallopeptidases, with an active site sequence motif of HEXXHXXGXH [164].…”

Section: Metallopeptidasesmentioning

confidence: 99%

Biological Roles of Peptidases in Trypanosomatids~!2009-11-26~!2010-02-15~!2010-03-18~!

Vermelho

Branquinha²,

d’Avila-Levy³

et al. 2010

TOPARAJ

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Abstract:In this review, we report the recent developments in the characterization of peptidases and their possible biological functions in the Trypanosomatidae family. The focus will be on peptidases from Trypanosoma cruzi, Leishmania spp., African trypanosomes and plant and insect trypanosomatids. There are numerous events in parasite development where the involvement of peptidases has been established, and they will be approached in the present review. Also in this review we will discuss the central roles have been proposed for peptidases in diverse processes such as virulence, host cell interaction and invasion, catabolism of host proteins, differentiation, cell cycle progression and both stimulation and evasion of host immune responses.

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Genes encoding the major surface glycoprotein in Leishmania are tandemly linked at a single chromosomal locus and are constitutively transcribed

Cited by 124 publications

References 36 publications

Coupling of poly(A) site selection and trans-splicing in Leishmania.

Coupling of poly(A) site selection and trans-splicing in Leishmania.

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

Biological Roles of Peptidases in Trypanosomatids~!2009-11-26~!2010-02-15~!2010-03-18~!

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