Characterisation of two Toxoplasma PROPPINs homologous to Atg18/WIPI suggests they have evolved distinct specialised functions

• Published in: PloS one Vol. 13; no. 4; p. e0195921
• Main Authors: Nguyen, Hoa Mai, Liu, Shuxian, Daher, Wassim, Tan, Feng, Besteiro, Sébastien
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.04.2018; Public Library of Science (PLoS)
• Subjects: Amino Acid Sequence; Autophagy; Autophagy (Cytology); Autophagy - genetics; Autophagy-Related Proteins - chemistry; Autophagy-Related Proteins - genetics; Autophagy-Related Proteins - metabolism; Biology and Life Sciences; Biosynthesis; Cell death; Cell Line; Cluster Analysis; Endoplasmic reticulum; Evolution, Molecular; Fitness; Functional analysis; Genetic aspects; Genome, Protozoan; Genomes; Growth conditions; Homeostasis; Homology; Humans; Lipids; Localization; Machinery and equipment; Medicine and Health Sciences; Multigene Family; Mutation; Open Reading Frames; Parasites; Parasitology; Phagocytosis; Protein Binding; Protein Multimerization; Protein Transport; Proteins; Protozoan Proteins - chemistry; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Rodents; Stress; Stress, Physiological - genetics; Stresses; Toxoplasma; Toxoplasma - genetics; Toxoplasma - metabolism; Toxoplasma gondii; Viability; France; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0195921

Toxoplasma gondii is a parasitic protist possessing a limited set of proteins involved in the autophagy pathway, a self-degradative machinery for protein and organelle recycling. This distant eukaryote has even repurposed part of this machinery, centered on protein ATG8, for a non-degradative function related to the maintenance of the apicoplast, a parasite-specific organelle. However, some evidence also suggest Toxoplasma is able to generate autophagic vesicles upon stress, and that some autophagy-related proteins, such as ATG9, might be involved solely in the canonical autophagy function. Here, we have characterised TgPROP1 and TgPROP2, two Toxoplasma proteins containing WD-40 repeat that can bind lipids for their recruitment to vesicular structures upon stress. They belong to the PROPPIN family and are homologues to ATG18/WIPI, which are known to be important for the autophagic process. We conducted a functional analysis of these two Toxoplasma PROPPINs. One of them is dispensable for normal in vitro growth, although it may play a role for parasite survival in specific stress conditions or for parasite fitness in the host, through a canonical autophagy-related function. The other, however, seems important for parasite viability in normal growth conditions and could be primarily involved in a non-canonical function. These divergent roles for two proteins from the same family illustrate the functional versatility of the autophagy-related machinery in Toxoplasma.