Legionella pneumophila modulates the host cytoskeleton by an effector of transglutaminase activity

TL;DR

This paper shows how Legionella pneumophila uses a protein called RavJ to alter the host cell's actin structure, aiding bacterial survival.

Contribution

The study identifies RavJ as a transglutaminase effector that crosslinks actin and Angiomotin proteins to manipulate host cell dynamics.

Findings

RavJ induces F-actin accumulation in host cells by crosslinking actin with Angiomotin family proteins.

RavJ crosslinks actin at Gln354 of Angiomotin, reducing actin-cofilin binding and inhibiting actin depolymerization.

LegL1 antagonizes RavJ's activity, decreasing actin-Motin crosslinks and modulating cytoskeletal dynamics.

Abstract

The bacterial pathogen Legionella pneumophila delivers more than 330 effector proteins into host cells through its Dot/Icm type IV secretion system (T4SS) to facilitate its intracellular replication. A number of these effectors modulate organelle trafficking pathways to create a membrane‐bound niche called the Legionella‐containing vacuole (LCV). In this study, we found that L. pneumophila induces F‐actin accumulation in the host cell cortex by its Dot/Icm substrate RavJ (Lpg0944). RavJ harbors a C101H138D170 motif associated with human tissue transglutaminases (TGs). We show that RavJ catalyzes a covalent linkage between actin and members of the Motin family of proteins, including Angiomotin (AMOT) and Angiomotin‐like 1 (AMOTL1), which are known to regulate cell migration and contribute to the formation of cellular structures such as endothelial cell junctions and tubes. Further study reveals that RavJ‐induced crosslink between actin and AMOT occurs on its Gln354 residue. Crosslink between actin and AMOT significantly reduces the binding between actin and its binding partner cofilin, suggesting that RavJ inhibits actin depolymerization. We also demonstrate that the metaeffector LegL1 directly interacts with RavJ to antagonize its TG activity, leading to reduced crosslinks between actin and Motin proteins. Our results reveal a novel mechanism of modulating the host actin cytoskeleton by L. pneumophila.

This study uncovers a novel mechanism by which Legionella pneumophila manipulates host cell actin dynamics. We show that the bacterial effector RavJ catalyzes a covalent crosslink between actin and the Angiomotin (AMOT) family of proteins, which are crucial for cell migration and cytoskeleton structural organization. RavJ‐induced crosslink impacts actin turnover to alter host cell behavior for the creation of a niche permissive for bacterial replication. The identification of RavJ as a transglutaminase (TG) has provided new insights into how Legionella exploits host cell machinery, which may facilitate functional studies of other TGs and offer potential avenues for therapeutic intervention.

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