DIMNP, UMR5235 CNRS - Université de Montpellier, Montpellier, France.
Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
PLoS One. 2018 Apr 16;13(4):e0195921. doi: 10.1371/journal.pone.0195921. eCollection 2018.
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.
刚地弓形虫是一种寄生的原生动物,拥有一套有限的参与自噬途径的蛋白质,这是一种用于蛋白质和细胞器回收的自我降解机制。这种遥远的真核生物甚至重新利用了这个机制的一部分,以蛋白 ATG8 为中心,用于与顶质体(一种寄生虫特有的细胞器)维持相关的非降解功能。然而,一些证据也表明,弓形虫在应激时能够产生自噬小泡,并且一些与自噬相关的蛋白质,如 ATG9,可能仅参与经典的自噬功能。在这里,我们对 TgPROP1 和 TgPROP2 这两种含有 WD-40 重复的弓形虫蛋白进行了特征描述,它们可以结合脂质,以便在应激时将其募集到囊泡结构中。它们属于 PROPPIN 家族,与 ATG18/WIPI 同源,后者已知对自噬过程很重要。我们对这两种弓形虫 PROPPIN 进行了功能分析。其中一种对于体外正常生长是可有可无的,尽管它可能在特定应激条件下对寄生虫的生存或在宿主中对寄生虫的适应性发挥作用,通过经典的与自噬相关的功能。然而,另一种对于正常生长条件下寄生虫的存活似乎很重要,并且可能主要涉及非经典功能。同一家族的两种蛋白质的这些不同作用说明了自噬相关机制在弓形虫中的功能多样性。