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Ecto-nucleotidases and Ecto-phosphatases from Leishmania and Trypanosoma Parasites

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Proteins and Proteomics of Leishmania and Trypanosoma

Part of the book series: Subcellular Biochemistry ((SCBI,volume 74))

Abstract

Ecto-enzymes can be defined as membrane-bound proteins that have their active site facing the extracellular millieu. In trypanosomatids, the physiological roles of these enzymes remain to be completed elucidated; however, many important events have already been related to them, such as the survival of parasites during their complex life cycle and the successful establishment of host infection. This chapter focuses on two remarkable classes of ecto-enzymes: ecto-nucleotidases and ecto-phosphatases, summarizing their occurrence and possible physiological roles in Leishmania and Trypanosoma genera. Ecto-nucleotidases are characterized by their ability to hydrolyze extracellular nucleotides, playing an important role in purinergic signaling. By the action of these ecto-enzymes, parasites are capable of modulating the host immune system, which leads to a successful parasite infection. Furthermore, ecto-nucleotidases are also involved in the purine salvage pathway, acting in the generation of nucleosides that are able to cross plasma membrane via specialized transporters. Another important ecto-enzyme present in a vast number of pathogenic organisms is the ecto-phosphatase. These enzymes are able to hydrolyze extracellular phosphorylated substrates, releasing free inorganic phosphate that can be internalized by the cell, crossing the plasma membrane through a Pi-transporter. Ecto-phosphatases are also involved in the invasion and survival of parasite in the host cells. Several alternative functions have been suggested for these enzymes in parasites, such as participation in their proliferation, differentiation, nutrition and protection. In this context, the present chapter provides an overview of recent discoveries related to the occurrence of ecto-nucleotidase and ecto-phosphatase activities in Leishmania and Trypanosoma parasites.

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Abbreviations

2′NMP:

Nucleoside 2′monophosphate

3′AMP:

Adenosine 3′monophosphate

3′NMP:

Nucleoside 3′monophosphate

5′(deoxy)NMP:

Deoxynucleoside 5′monophosphate

ACR:

Apyrase conserved region

ADO:

Adenosine

ADP:

Adenosine diphosphate

AMP:

Adenosine monophosphate

ATP:

Adenosine triphosphate

cAMP:

Cyclic adenosine monophosphate

cGMP:

Cyclic guanosine monophosphate

CMP:

Cytosine monophosphate

CTP:

Cytosine triphosphate

DC:

Dendritic cell

DIDS:

4,4′-diisothiocyanostylbene 2′-2′-disulfonic acid

DNA:

Deoxyribonucleic acid

Ecto-3′NT/NU:

Ecto-3′nucleotidase/nuclease

Ecto-5′NT:

Ecto-5′nucleotidase

E-NPP:

Ecto-nucleotide pyrophosphatase/phosphodiesterase

E-NTPDase:

Ectonucleoside triphosphate diphosphohydrolase

GMP:

Guanosine monophosphate

GPI:

Glycosyl phosphatidyl inositol

GTP:

Guanosine triphosphate

IFN-γ:

Interferon-γ

IL:

Interleukine

IMP:

Inosine monophosphate

ITP:

Inosine triphosphate

NDP:

Nucleoside diphosphate

NO:

Nitric oxide

NTP:

Nucleoside triphosphate

P1:

Adenosine receptor

P2:

ATP receptor

PFTM:

Purine free trypanosome medium

PHO pathway:

Phosphate signal-transduction pathway

PHP:

Phosphohistidine phosphatase

Pi:

Inorganic phosphate

PP:

Phosphoserine/threonine phosphatase

PTP:

Phosphotyrosine phosphatase

RNA:

Ribonucleic acid

ROS:

Reactive oxygen species

TNF-α:

Tumor necrosis factor-α

TTP:

Thymidine triphosphate

TYR:

Tyrosine

UDP:

Uridine diphosphate

UMP:

Uridine monophosphate

UTP:

Uridine triphosphate

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Freitas-Mesquita, A.L., Meyer-Fernandes, J.R. (2014). Ecto-nucleotidases and Ecto-phosphatases from Leishmania and Trypanosoma Parasites. In: Santos, A., Branquinha, M., d’Avila-Levy, C., Kneipp, L., Sodré, C. (eds) Proteins and Proteomics of Leishmania and Trypanosoma. Subcellular Biochemistry, vol 74. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7305-9_10

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