A Plasmodium falciparum S33 proline aminopeptidase is associated with changes in erythrocyte deformability

• Published in: Experimental parasitology 2016-10, Vol.169, p.13-21
• Main Authors: da Silva, Fabio L., Dixon, Matthew W.A., Stack, Colin M., Teuscher, Franka, Taran, Elena, Jones, Malcolm K., Lovas, Erica, Tilley, Leann, Brown, Christopher L., Trenholme, Katharine R., Dalton, John P., Gardiner, Donald L., Skinner-Adams, Tina S.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Aminopeptidases - chemistry; Aminopeptidases - genetics; Aminopeptidases - immunology; Aminopeptidases - metabolism; Antibodies, Protozoan - immunology; Blotting, Northern; Blotting, Western; Cell Adhesion - physiology; Cytoadherence; Elasticity; Erythrocyte deformability; Erythrocyte Deformability - physiology; Erythrocyte Membrane - genetics; Erythrocyte Membrane - physiology; Erythrocytes - parasitology; Gene Knockout Techniques; Humans; Malaria; Microscopy, Atomic Force; Microscopy, Electron, Transmission; Microscopy, Fluorescence; Plasmodium falciparum; Plasmodium falciparum - enzymology; Plasmodium falciparum - genetics; Prolyl aminopeptidase; Real-Time Polymerase Chain Reaction; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Recombinant Proteins - metabolism; RNA, Protozoan - chemistry; Sequence Alignment; Transfection
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2016.06.013

Infection with the apicomplexan parasite Plasmodium falciparum is a major cause of morbidity and mortality worldwide. One of the striking features of this parasite is its ability to remodel and decrease the deformability of host red blood cells, a process that contributes to disease. To further understand the virulence of Pf we investigated the biochemistry and function of a putative Pf S33 proline aminopeptidase (PfPAP). Unlike other P. falciparum aminopeptidases, PfPAP contains a predicted protein export element that is non-syntenic with other human infecting Plasmodium species. Characterization of PfPAP demonstrated that it is exported into the host red blood cell and that it is a prolyl aminopeptidase with a preference for N-terminal proline substrates. In addition genetic deletion of this exopeptidase was shown to lead to an increase in the deformability of parasite-infected red cells and in reduced adherence to the endothelial cell receptor CD36 under flow conditions. Our studies suggest that PfPAP plays a role in the rigidification and adhesion of infected red blood cells to endothelial surface receptors, a role that may make this protein a novel target for anti-disease interventions strategies. [Display omitted] •The pathology of Falciparum malaria is associated with the remodeling of host RBCs.•We investigated the role of PfPAP, a putative proline aminopeptidase in this process.•PfPAP contains a predicted protein export element and is non-syntenic with other malaria species.•Our data confirm that PfPAP is a proline aminopeptidase that it is exported into the host RBC.•Genetic deletion of PfPAP suggests it plays a role in RBC rigidification and cytoadhesion