Localization and phosphorylation of Plasmodium falciparum nicotinamide/nicotinate mononucleotide adenylyltransferase (PfNMNAT) in intraerythrocytic stages

• Published in: Malaria journal Vol. 17; no. 1; p. 161
• Main Authors: Nieto, Carlos A, Sánchez, Lina M, Sánchez, Diana M, Díaz, Gonzalo J, Ramírez, María H
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11-04-2018; BioMed Central; BMC
• Subjects: Animals; Chickens - parasitology; Diagnosis; Erythrocytes - parasitology; Humans; Immunolocalization; Malaria; Mice - parasitology; NAD (Coenzyme); NAD+ metabolism; Nicotinamide-Nucleotide Adenylyltransferase - metabolism; PfNMNAT; Phosphorylation; Plasmodium falciparum; Plasmodium falciparum - physiology; Risk factors; Immunolocalization; Plasmodium falciparum; Phosphorylation; Malaria; PfNMNAT; NAD+ metabolism
• ISSN: 1475-2875; 1475-2875
• DOI: 10.1186/s12936-018-2307-4

Nicotinamide adenine dinucleotide (NAD+) is an essential molecule in the energy metabolism of living beings, and it has various cellular functions. The main enzyme in the biosynthesis of this nucleotide is nicotinamide/nicotinate mononucleotide adenylyltransferase (NMNAT, EC 2.7.7.1/18) because it is the convergence point for all known biosynthetic pathways. NMNATs have divergences in both the number of isoforms detected and their distribution, depending on the organism.
In the laboratory of basic research in biochemistry (LIBBIQ: acronym in Spanish) the NMNATs of protozoan parasites (Leishmania braziliensis, Plasmodium falciparum, Trypanosoma cruzi, and Giardia duodenalis) have been studied, analysing their catalytic properties through the use of proteins. Recombinants and their cellular distribution essentially. In 2014, O'Hara et al. determined the cytoplasmic localization of NMNAT of P. falciparum, using a transgene coupled to GFP, however, the addition of labels to the study protein can modify several of its characteristics, including its sub-cellular localization.
This study confirms the cytoplasmic localization of this protein in the parasite through recognition of the endogenous protein in the different stages of the asexual life cycle. Additionally, the study found that PfNMNAT could be a phosphorylation target at serine, tyrosine and threonine residues, and it shows variations during the asexual life cycle.
These experiments confirmed that the parasite is situated in the cytoplasm, fulfilling the required functions of NAD+ in this compartment, the PfNMNAT is regulated in post-transcription processes, and can be regulated by phosphorylation in its residues.