Tanaka Shino, Oide Hiromu, Ikeda Shumma, Tagaya Mitsuo, Nagai Hiroki, Kubori Tomoko, Arasaki Kohei
School of Life Sciences, Tokyo University of Pharmacy and Life Sciences , Hachioji, Japan.
Department of Microbiology, Graduate School of Medicine, Gifu University, Gifu, Japan.
J Cell Biol. 2025 Apr 7;224(4). doi: 10.1083/jcb.202406159. Epub 2025 Mar 4.
Legionella pneumophila is an intracellular bacterial pathogen that modulates membrane trafficking to survive and proliferate within host cells. After phagocytosis, the L. pneumophila-containing vacuole evades the endocytic pathway by excluding the host GTPase Rab5, a crucial regulator of phagosomal maturation. In this study, we show that the evolutionarily conserved lysine residue K134 of Rab5 undergoes ubiquitination during infection. This modification depends on Lpg2525, an F-box protein from L. pneumophila that acts as a component of the SKP-Cullin-F-box complex. We further demonstrate that Rab5 ubiquitination facilitates the recruitment of RabGAP-5, a Rab5-specific GAP, leading to Rab5 inactivation and subsequent release from the bacterial vacuole. Importantly, the K134 Rab5 mutant limits L. pneumophila replication within host cells. These findings reveal that Lpg2525-mediated Rab5 ubiquitination is a key survival strategy employed by L. pneumophila in infected host cells.
嗜肺军团菌是一种细胞内细菌病原体，它通过调节膜运输在宿主细胞内存活和增殖。吞噬作用后，含有嗜肺军团菌的液泡通过排除宿主GTP酶Rab5（吞噬体成熟的关键调节因子）来逃避内吞途径。在本研究中，我们表明Rab5进化上保守的赖氨酸残基K134在感染过程中发生泛素化。这种修饰依赖于Lpg2525，一种来自嗜肺军团菌的F-box蛋白，它作为SKP-Cullin-F-box复合物的一个组成部分发挥作用。我们进一步证明，Rab5泛素化促进了Rab5特异性GAP RabGAP-5的募集，导致Rab5失活并随后从细菌液泡中释放。重要的是，K134 Rab5突变体限制了嗜肺军团菌在宿主细胞内的复制。这些发现揭示了Lpg2525介导的Rab5泛素化是嗜肺军团菌在感染宿主细胞中采用的一种关键生存策略。
