Ecto-nucleotidases and Ecto-phosphatases from Leishmania and Trypanosoma Parasites
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 alread
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Ecto-nucleotidases and Ecto-phosphatases from Leishmania and Trypanosoma Parasites Anita Leocadio Freitas-Mesquita and José Roberto Meyer-Fernandes
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.
A.L. Freitas-Mesquita • J.R. Meyer-Fernandes (*) Medical Biochemistry Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil e-mail: [email protected] A.L.S. Santos et al. (eds.), Proteins and Proteomics of Leishmania and Trypanosoma, Subcellular Biochemistry 74, DOI 10.1007/978-94-007-7305-9_10, © Springer Science+Business Media Dordrecht 2014
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Abbreviations 2′NMP 3′AMP 3′NMP 5′(deoxy)NMP ACR ADO ADP AMP ATP cAMP cGMP CMP CTP DC DIDS DNA Ecto-3′NT/NU Ecto-5′NT E-NPP E-NTPDase GMP GPI GTP IFN-γ IL IMP ITP NDP NO NTP P1 P2 PFTM PHO pathway PHP Pi PP PTP RNA ROS TNF-α TTP TYR
Nucleoside 2′monophosphate Adenosine 3′monophosphate Nucleoside 3′monophosphate Deoxynucleoside 5′monophosphate Apyrase conserved region Adenosine Adenosine diphosphate Adenosine monophosphate Adenosine triphosphate Cyclic adenosine monophosphate Cyclic guanosine monophosphate Cytosine monophosphate Cytosine triphosphate Dendritic cell 4,4′-diisothiocyanostylbene 2′-2′-disulfonic acid De
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