Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Eppendorf, Hamburg, Germany.
Leibniz Institute for Molecular Pharmacology, Berlin, Germany.
J Cell Biol. 2019 Sep 2;218(9):3039-3059. doi: 10.1083/jcb.201812106. Epub 2019 Jul 23.
The spirochete , the causative agent of Lyme disease, is internalized by macrophages and processed in phagolysosomes. Phagosomal compaction, a crucial step in phagolysosome maturation, is driven by contact of Rab5a-positive vesicles with the phagosomal coat. We show that the sorting nexin SNX3 is transported with Rab5a vesicles and that its PX domain enables vesicle-phagosome contact by binding to PI(3)P in the phagosomal coat. Moreover, the C-terminal region of SNX3 recruits galectin-9, a lectin implicated in protein and membrane recycling, which we identify as a further regulator of phagosome compaction. SNX3 thus forms a hub for two distinct vesicle populations, constituting a convergence point for the endosomal recycling machinery, to contribute to phagosome maturation and intracellular processing of borreliae. These data also suggest that the helical shape of itself, providing sites of high curvature and thus local PI(3)P enrichment at phagosomes, may be one of the driving elements underlying the efficient elimination of spirochetes by immune cells.
螺旋体是莱姆病的病原体，它被巨噬细胞内化，并在吞噬溶酶体中进行处理。吞噬体的浓缩是吞噬溶酶体成熟的关键步骤，是由 Rab5a 阳性囊泡与吞噬体被膜的接触驱动的。我们表明，分选连接蛋白 SNX3 与 Rab5a 囊泡一起运输，其 PX 结构域通过与吞噬体被膜中的 PI(3)P 结合，使囊泡与吞噬体接触。此外，SNX3 的 C 末端区域招募半乳糖凝集素-9，这是一种参与蛋白质和膜回收的凝集素，我们将其鉴定为吞噬体浓缩的另一个调节剂。因此，SNX3 形成了两个不同囊泡群体的枢纽，构成了内体回收机制的汇聚点，有助于吞噬体成熟和胞内螺旋体的处理。这些数据还表明，其自身的螺旋形状可能是免疫细胞有效清除螺旋体的驱动因素之一，因为它提供了高曲率的部位，从而在吞噬体中局部富集 PI(3)P。
