Knockdown of the translocon protein EXP2 in Plasmodium falciparum reduces growth and protein export

• Published in: PloS one Vol. 13; no. 11; p. e0204785
• Main Authors: Charnaud, Sarah C, Kumarasingha, Rasika, Bullen, Hayley E, Crabb, Brendan S, Gilson, Paul R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.11.2018; Public Library of Science (PLoS)
• Subjects: Antigens; Attenuation; Biology and Life Sciences; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell cycle; Dihydrofolate reductase; Erythrocytes; Erythrocytes - metabolism; Erythrocytes - parasitology; Exports; Gene expression; Gene Knockdown Techniques; Humans; Immune system; Immunology; Life Cycle Stages - genetics; Malaria; Medicine and Health Sciences; Nutrients; Parasites; Plasmodium falciparum; Plasmodium falciparum - genetics; Plasmodium falciparum - growth & development; Protein transport; Protein Transport - genetics; Proteins; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Reduction; Vector-borne diseases; Australia; Victoria Australia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0204785

Malaria parasites remodel their host erythrocytes to gain nutrients and avoid the immune system. Host erythrocytes are modified by hundreds of effector proteins exported from the parasite into the host cell. Protein export is mediated by the PTEX translocon comprising five core components of which EXP2 is considered to form the putative pore that spans the vacuole membrane enveloping the parasite within its erythrocyte. To explore the function and importance of EXP2 for parasite survival in the asexual blood stage of Plasmodium falciparum we inducibly knocked down the expression of EXP2. Reduction in EXP2 expression strongly reduced parasite growth proportional to the degree of protein knockdown and tended to stall development about half way through the asexual cell cycle. Once the knockdown inducer was removed and EXP2 expression restored, parasite growth recovered dependent upon the length and degree of knockdown. To establish EXP2 function and hence the basis for growth reduction, the trafficking of an exported protein was monitored following EXP2 knockdown. This resulted in severe attenuation of protein export and is consistent with EXP2, and PTEX in general, being the conduit for export of proteins into the host compartment.