Crithidia fasciculata contains a transcribed leishmanial surface proteinase (gp63) gene homologue

Inverso, J A; Medina‐Acosta, Enrique; O'Connor, Jack; Russell, David G.; Cross, George A.M.

doi:10.1016/0166-6851(93)90242-p

Cited by 53 publications

(30 citation statements)

References 34 publications

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“…The GP63 cDNA hybridizes strongly to a 3-kb RNA in bloodstream trypanosomes and only weakly to the same sized RNA in procyclic trypanosomes. The 3-kb size is consistent with the 2786 nucleotides in the GP63-1 cDNA and with the sizes of GP63 mRNAs in Lieshmania and Crithidia (24,51). As expected, the VSG and procyclin cDNAs hybridize predominantly to the bloodstream and procyclic RNAs, respectively, and the tubulin cDNA hybridizes about equally to both RNAs, indicating similar amounts of RNA were added to each lane.…”

Section: Identification Of T Brucei Cdnas Encoding Homologues Ofsupporting

confidence: 76%

“…The identification of an expressed GP63-like gene in C. fasciculata (24), a trypanosomatid whose life cycle is confined to insects, suggests that one of the main roles of GP63 for Leishmania occurs during the parasite's insect stages. Supporting this possibility is the finding that another protozoan parasite of insects, Herpetomonas samuelpessoai, also has a GP63-like metalloprotease activity on its surface (58,59).…”

Section: Discussionmentioning

confidence: 99%

“…A homologue of Leishmania GP63 has been reported in another trypanosomatid, Crithidia fasciculata (24). C. fasciculata is not known to infect a mammalian host.…”

mentioning

confidence: 99%

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African Trypanosomes Have Differentially Expressed Genes Encoding Homologues of the Leishmania GP63 Surface Protease

El-Sayed

Donelson

1997

Journal of Biological Chemistry

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The genomes of various Leishmania parasites contain tandemly arrayed genes encoding an abundant 63-kDa surface glycoprotein called GP63. Leishmania GP63s are metalloproteases that play an important role in the invasion and survival of the parasites within the macrophage, and their presence on the Leishmania surface has been correlated with resistance to complement-mediated lysis. Here we report the identification of GP63-like genes in African trypanosomes. The predicted trypanosome and Leishmania GP63s share a metalloprotease catalytic site motif of HEXXH as well as 19 cysteines and 10 prolines, implying a conservation of enzymatic activity and secondary/tertiary structure. The trypanosome GP63 genes are transcribed equally in procyclic and bloodstream trypanosomes, but their mRNAs accumulate to a 50-fold higher steady state level in bloodstream trypanosomes, where the ratio of mRNAs for GP63 and variant surface glycoprotein is about 1:150. Transcription of the GP63 genes is sensitive to ␣-amanitin, indicating that they are transcribed by a different polymerase than the variant surface glycoprotein genes. These results lead to a reconsideration of the potential functions of GP63, inasmuch as African trypanosomes are not known to interact with macrophages and do not have an intracellular stage during their life cycle.

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Section: Identification Of T Brucei Cdnas Encoding Homologues Ofsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

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African Trypanosomes Have Differentially Expressed Genes Encoding Homologues of the Leishmania GP63 Surface Protease

El-Sayed

Donelson

1997

Journal of Biological Chemistry

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“…It was also suggested that the primary role of the proteolytic activity of gp63 is related to the cleavage of host cell macromolecules, either for protection or to provide parasite nutrition (12). Its predominant expression in the promastigote form, together with the identification of homologues in monogenetic trypanosomatids like Crithidia fasciculata and Herpetomonas samuelpessoai (26,45), suggest that leishmanolysin may be important for the interaction with the invertebrate host. However, gp63 is apparently not essential for insect stages of the life cycle, as Leishmania major promastigotespecific genes can be deleted without deleterious effects on growth and development in the sandfly vector (27).…”

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confidence: 99%

gp63 Homologues inTrypanosoma cruzi: Surface Antigens with Metalloprotease Activity and a Possible Role in Host Cell Infection

2003

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gp63 is a highly abundant glycosylphosphatidylinositol (GPI)-anchored membrane protein expressed predominantly in the promastigote but also in the amastigote stage of Leishmania species. In Leishmania spp., gp63 has been implicated in a number of steps in establishment of infection. Here we demonstrate that Trypanosoma cruzi, the etiological agent of Chagas' disease, has a family of gp63 genes composed of multiple groups. Two of these groups, Tcgp63-I and -II, are present as high-copy-number genes. The genomic organization and mRNA expression pattern were specific for each group. Tcgp63-I was widely expressed, while the Tcgp63-II group was scarcely detected in Northern blots, even though it is well represented in the T. cruzi genome. Western blots using sera directed against a synthetic peptide indicated that the Tcgp63-I group produced proteins of ϳ78 kDa, differentially expressed during the life cycle. Immunofluorescence staining and phosphatidylinositol-specific phospholipase C digestion confirmed that Tcgp63-I group members are surface proteins bound to the membrane by a GPI anchor. We also demonstrate the presence of metalloprotease activity which is attributable, at least in part, to Tcgp63-I group. Since antibodies against Tcgp63-I partially blocked infection of Vero cells by trypomastigotes, a possible role for this group in infection is suggested.

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“…They form a multicopy family comprising approximately 7 genes. The deduced amino acid sequences show a great degree of conservation compared with leishmanial MSP (48). Metalloprotease activity has been detected using fibrinogen as a substrate, suggesting that the genes are functional in these protozoa (35).…”

Section: Tbmsp-bmentioning

confidence: 97%

Major Surface Protease of Trypanosomatids: One Size Fits All?

Yao

2010

Infect Immun

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Trypanosomatids are a very diverse group of protozoa including many species of medical, veterinary, and/or economical importance. Leishmania spp. cause disease on the continents of Asia, Africa, Europe, and North and South America; Trypanosoma cruzi is the etiology of Chagas' disease in South and Central America; and Trypanosoma brucei infections result in African sleeping sickness. Four genera of heteroxenous trypanosomatids transmitted by insect vectors infect a wide range of hosts including humans, animals, and plants. Six genera of monoxenous trypanosomatids parasitize numerous species of insects. Due to this diversity, the life cycle of Leishmania spp. is presented as a model to which other heteroxenous and monoxenous groups will be briefly contrasted.During their life cycle, Leishmania spp. shuttle between a flagellated promastigote stage in the sand fly vector and a nonmotile amastigote stage in a mammalian host. During blood meals on infected hosts, the sand fly vectors ingest amastigote-laden macrophages (Mø). These amastigotes transform to procyclic promastigotes in the sand fly gut, multiply by binary fission, and eventually develop into metacyclic promastigotes, the infective stage for mammalian hosts including humans. The sand fly vectors, upon taking another blood meal, inoculate the metacyclic promastigotes into the dermis, where they are phagocytized by Mø of the mammalian hosts. Amastigotes, transformed from metacyclic promastigotes, multiply in parasitophorous vacuoles (PV) of the host's Mø. Multiplication of amastigotes eventually leads to rupture of the infected Mø and release of amastigotes, which infect additional Mø, perpetuating the cycle of replication (38).Other , Crithidia, Leptomonas, Herpetomonas, Rhynchoidomonas, and Phytomonas (87). Leishmania spp. harbor a zinc metalloprotease, discovered in the mid-1980s, on their surfaces (14,15,36,37,88). This enzyme, accounting for about 1% of the total protein in promastigotes of Leishmania major and Leishmania mexicana (2, 10) and being potentially important during different stages of the life cycle, soon became the object of much investigation (8,70,71,107). Although referred to here as major surface protease (MSP), this zinc metalloprotease has also been termed GP63, surface acid protease, promastigote surface protease, EC 3.4.24.36, and leishmanolysin.MSPs of Leishmania spp. belong to the M8 family of endopeptidases, sharing several characteristics with mammalian matrix metalloproteases. Similarities include degradation of the extracellular matrix, cell surface localization, protease activity requiring Zn 2ϩ , and inhibition of protease activity by * Mailing address:

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Crithidia fasciculata contains a transcribed leishmanial surface proteinase (gp63) gene homologue

Cited by 53 publications

References 34 publications

African Trypanosomes Have Differentially Expressed Genes Encoding Homologues of the Leishmania GP63 Surface Protease

African Trypanosomes Have Differentially Expressed Genes Encoding Homologues of the Leishmania GP63 Surface Protease

gp63 Homologues inTrypanosoma cruzi: Surface Antigens with Metalloprotease Activity and a Possible Role in Host Cell Infection

Major Surface Protease of Trypanosomatids: One Size Fits All?

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