Subversion of the host endocytic pathway by Legionella pneumophila-mediated ubiquitination of Rab5.

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. © 2025 Tanaka et al.

Citation

Shino Tanaka, Hiromu Oide, Shumma Ikeda, Mitsuo Tagaya, Hiroki Nagai, Tomoko Kubori, Kohei Arasaki. Subversion of the host endocytic pathway by Legionella pneumophila-mediated ubiquitination of Rab5. The Journal of cell biology. 2025 Apr 07;224(4)

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PMID: 40035702

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