Cell entry of a host-targeting protein of oomycetes requires gp96.

The animal-pathogenic oomycete Saprolegnia parasitica causes serious losses in aquaculture by infecting and killing freshwater fish. Like plant-pathogenic oomycetes, S. parasitica employs similar infection structures and secretes effector proteins that translocate into host cells to manipulate the host. Here, we show that the host-targeting protein SpHtp3 enters fish cells in a pathogen-independent manner. This uptake process is guided by a gp96-like receptor and can be inhibited by supramolecular tweezers. The C-terminus of SpHtp3 (containing the amino acid sequence YKARK), and not the N-terminal RxLR motif, is responsible for the uptake into host cells. Following translocation, SpHtp3 is released from vesicles into the cytoplasm by another host-targeting protein where it degrades nucleic acids. The effector translocation mechanism described here, is potentially also relevant for other pathogen–host interactions as gp96 is found in both animals and plants. The pathogenic oomycete Saprolegnia parasitica secretes effector proteins that translocate into host cells through unclear mechanisms. Here, Trusch et al. show that the uptake of effector protein SpHtp3, resulting in RNA degradation, depends on a gp96-like host receptor and a second effector protein.

动物致病性卵菌寄生水霉通过感染和杀死淡水鱼在水产养殖中造成严重损失。与植物致病性卵菌一样，寄生水霉采用类似的感染结构并分泌效应蛋白，这些效应蛋白转移到宿主细胞中以操控宿主。在此，我们表明宿主靶向蛋白SpHtp3以一种不依赖病原体的方式进入鱼细胞。这种摄取过程由一种类gp96受体引导，并且可被超分子镊子抑制。SpHtp3的C末端（包含氨基酸序列YKARK），而非N末端的RxLR基序，负责被宿主细胞摄取。在转移之后，SpHtp3被另一种宿主靶向蛋白从囊泡释放到细胞质中，在那里它降解核酸。此处描述的效应蛋白转移机制可能也与其他病原体 - 宿主相互作用有关，因为gp96在动物和植物中均有发现。 致病性卵菌寄生水霉分泌效应蛋白，这些效应蛋白通过不明确的机制转移到宿主细胞中。在此，特鲁施等人表明效应蛋白SpHtp3的摄取（导致RNA降解）依赖于一种类gp96宿主受体和第二种效应蛋白。